Propionic acid (8R,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester BDBM50215709 testosteron propionate Propionic acid 10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester(Testosterone Propionate) CHEMBL1170 Propionic acid 10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl ester TESTOSTERONE PROPIONATE
BDBM50257201 CHEMBL500826 sodium propionate
7A-Methyl-Testosterone BDBM50423527 CHEMBL359619 7Alpha-Methyl-Testosterone
BDBM589230 US11554172, Compound Fluticasone-Propionate
cid_32798 SMR000058745 MLS000028708 CLOBETASOL PROPIONATE BDBM39347
Isosorbide-2-benzylcarbamate-5-propionate BDBM50252783 CHEMBL493672
4-Methyl-Testosterone BDBM50423534 CHEMBL265925
6Alpha-Methyl-Testosterone CHEMBL260640 BDBM50423520
9A-Fluoro-Testosterone BDBM50423524 CHEMBL259599
BDBM50423514 CHEMBL411316 16Alpha-Hydroxy-Testosterone
Ethyl-3-borono-2-(carbamylamino)propionate BDBM50010600 CHEMBL168878
SODIUM LACTATE CHEMBL1357 Sodium; 2-hydroxy-propionate BDBM50159794
3-(2-hydroxyphenyl)propionic acid 3-(2-Hydroxyphenyl)propionate BDBM36128
3-(2-hydroxyphenyl)propionic acid 3-(2-Hydroxyphenyl)propionate BDBM36144
3-(4-hydroxyphenyl)propionic acid 3-(4-Hydroxyphenyl)propionate BDBM36143
BDBM36129 3-(4-hydroxyphenyl)propionic acid 3-(4-Hydroxyphenyl)propionate
CCI-18781 Flonase Flovent diskus 50 FLUTICASONE PROPIONATE BDBM50354849 US10869929, Compound FLUTICASONE PROPIONATE Flovent hfa Flovent diskus 250 Cutivate Fluticasone Flovent Flovent diskus 100
sodium;2-(2-quinolinylthio)propanoate Sodium; 2-(quinolin-2-ylsulfanyl)-propionate cid_23663723 BDBM114319 sodium;2-(2-quinolylthio)propionate MLS000555430 sodium;2-quinolin-2-ylsulfanylpropanoate SMR000147147
4-(2-(6-phenylpicolinamido)acetyl)piperazin-1-yl propionate BDBM50298124 CHEMBL549307
BDBM50298122 CHEMBL549797 4-(2-(4,6-diphenylpicolinamido)acetyl)piperazin-1-yl propionate
(1S,2R,10R,11S,14S,15S)-14-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one Testosterone US9682960, Testosterone Testosterone, 1 BDBM8885 17beta-Hydroxyandrost-4-en-3-one
BDBM50022201 Sodium; 3-{hydroxy-[3-(naphthalen-2-ylmethoxy)-phenyl]-carbamoyl}-propionate CHEMBL34676
BDBM50023537 Sodium; 3-{bis-[4-(2,2-dimethyl-propionyloxy)-phenyl]-methoxycarbonyl}-propionate CHEMBL10148
CHEMBL1169703 BDBM50322032 2-Methylisoindole-1,3-dione-5-yl 3-(4-aminophenyl)propionate
BDBM50075091 CHEMBL131894 Sodium; 3-{2-[(4-chloro-benzenesulfonylamino)-methyl]-indan-5-yl}-propionate
loxoprofen sodium CHEMBL66552 BDBM50330853 Sodium; 2-[4-(2-oxo-cyclopentylmethyl)-phenyl]-propionate; hydrate
CHEMBL1171655 2-Methylisoindole-1,3-dione-5-yl 3-(6-aminopyridin-3-yl)propionate BDBM50322033
2-(4-Cyanophenyl)isoindole-1,3-dione-5-yl(E)-3-(4-aminophenyl)propionate CHEMBL1172717 BDBM50322034
dilithium; 3-((2-carboxy-ethylsulfanyl)-{3-[(quinoline-2-carbonyl)-amino]-phenyl}-methylsulfanyl)-propionate CHEMBL338166 BDBM50001295
17-Hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one (testosterone)17-Hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one testosterone CHEMBL386630 17-Hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one(testosterone) BDBM50025452 14-hydroxy-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-6-en-5-one 17-Hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one (Testosterone)
BDBM50265314 CHEMBL497586 3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropyl propionate
CHEMBL15481 Sodium; 3-{1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-phenyl-propylsulfanyl}-propionate BDBM50280700
CHEMBL343392 Sodium; 3-[3-hydroxycarbamoyl-2-(4-methoxy-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl]-propionate BDBM50082478
BDBM50025453 CHEMBL3349127 Sodium; 2-(4a,6a-dimethyl-2-oxo-hexadecahydro-indeno[5,4-f]quinolin-7-yl)-propionate
BDBM50077371 Sodium; 3-[(R)-3-hydroxycarbamoyl-2-(4-methoxy-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl]-propionate CHEMBL56965
Sodium; 2-(1,4a,6a-trimethyl-2-oxo-hexadecahydro-indeno[5,4-f]quinolin-7-yl)-propionate BDBM50025401 CHEMBL3085568
3-(trifluoromethyl)-5-(4-((1R,2R)-2-(4-(trifluoromethyl)phenyl)cyclopropanecarbonyl)piperazin-1-ylsulfonyl)phenyl propionate BDBM50267616 CHEMBL488932
BDBM50280715 Sodium; 3-[1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-(2-dimethylcarbamoyl-phenyl)-propylsulfanyl]-propionate CHEMBL15513
CHEMBL15292 BDBM50280694 Sodium; 3-[1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-(2-sulfamoyl-phenyl)-propylsulfanyl]-propionate
CHEMBL563301 methyl 3-(3-(3(3-fluoro-4hydroxyphenyl)-4,5-dihydroisoxazole-5-yl)-1,2,4-oxadiazol-5-yl)propionate BDBM50298011
Erythromycin Estolate Erythromycin Propionate Lauryl Sulfate CHEBI:4846 BDBM50237591 Ilosone Erythromycin Lauryl Sulfate, Propionyl Propionyl Erythromycin Lauryl Sulfate
Erythromycin Estolate Erythromycin Propionate Lauryl Sulfate CHEBI:4846 Ilosone Erythromycin Lauryl Sulfate, Propionyl Propionyl Erythromycin Lauryl Sulfate BDBM50103515
Sodium; 3-[1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-(2-methanesulfonylamino-phenyl)-propylsulfanyl]-propionate CHEMBL274049 BDBM50280698
[2-[(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methoxy]methyl propionate (14b) BDBM234289
Sodium; 3-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-isopropyl-1H-indol-2-yl]-2,2-dimethyl-propionate(Takeda AA 861) CHEMBL416657 Sodium; 3-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-isopropyl-1H-indol-2-yl]-2,2-dimethyl-propionate BDBM50000838
3-phenyl-2-(trimethylazaniumyl)propanoate MLS000863632 3-phenyl-2-(trimethylammonio)propionate cid_16745393 BDBM76196 SMR000440709 3-phenyl-2-(trimethylammonio)propanoate
BDBM50264743 (S)-1-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-3-phenylpropan-2-yl propionate CHEMBL490424
US10836743, Compound A7 Methyl 3-(4-fluoro-4-(((trans-2-phenylcyclo- propyl)amino)methyl)piperidin-1- yl)-propionate BDBM472868
Sodium;3-[(R)-{3-[(E)-2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-(2-dimethylcarbamoyl-ethylsulfanyl)-methylsulfanyl]-propionate MK-679 BDBM50052029 Sodium; 3-[(R)-{3-[(E)-2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-(2-dimethylcarbamoyl-ethylsulfanyl)-methylsulfanyl]-propionate L-668019 CHEMBL89340
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl) BDBM50019951
BDBM561980 methyl 3-[6-[(Z)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydro isoquinolin-2-yl]propionate US11396495, No. 57
CHEMBL15419 BDBM50280692 Sodium; 3-[1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-(2-isopropyl-phenyl)-propylsulfanyl]-2-methyl-propionate
CHEMBL278411 Sodium; 3-{1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-[2-(piperidine-1-carbonyl)-phenyl]-propylsulfanyl}-propionate BDBM50280689
Sodium; 3-[1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-(2-nitro-phenyl)-propylsulfanyl]-2-methyl-propionate CHEMBL15370 BDBM50280693
methyl 3-[6-[(E)-2-(aminomethyl)-3-fluoro-allyloxy]-1-oxo-3,4-dihydro isoquinolin-2-yl]propionate BDBM561979 US11396495, No. 56
BDBM50106099 CHEMBL321739 Lithium; (S)-3-[2-((3-methyl-butyl)-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-amino)-acetylamino]-3-phenyl-propionate
CHEMBL14819 Sodium; 3-{1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-[2-(2H-[1,2,4]triazol-3-yl)-phenyl]-propylsulfanyl}-propionate BDBM50280712
BDBM50096894 Sodium; 3-cyclohexyl-2-{2,3,5-trihydroxy-6-[2-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-tetrahydro-pyran-4-yloxy}-propionate CHEMBL3215408 Sodium; (R)-3-cyclohexyl-2-{3,5-dihydroxy-2-hydroxymethyl-6-[2-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-tetrahydro-pyran-4-yloxy}-propionate
(3R,5S)-5-((4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidin-3-yl propionate BDBM50293258 CHEMBL500381
BDBM50025427 CHEMBL3349153 Sodium; 2-(1,4a,6a-trimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno[5,4-f]quinolin-7-yl)-propionate
CHEMBL3349157 BDBM50025422 Sodium; 2-(4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno[5,4-f]quinolin-7-yl)-propionate
Sodium; 2-(1,4a,6a-trimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-1H-indeno[5,4-f]quinolin-7-yl)-propionate BDBM50025352 CHEMBL3349083
(RS)-2-amino-3-(1-hydroxy-1,2,3-triazol-5-yl)propionate BDBM50107950 CHEMBL321164 2-Amino-3-(3-hydroxy-3H-[1,2,3]triazol-4-yl)-propionic acid
BDBM50096895 CHEMBL3215404 Sodium; (S)-3-phenyl-2-{2,3,5-trihydroxy-6-[2-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-tetrahydro-pyran-4-yloxy}-propionate
Methyl (R)-3-((5-(1-amino-8-azaspiro[4.5]decan-8-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)thio)propionate US11498930, Compound 1.2.24 BDBM580319
BDBM50096893 CHEMBL356673 Sodium; 2-{2-benzoylamino-3,5-dihydroxy-6-[2-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-tetrahydro-pyran-4-yloxy}-3-phenyl-propionate
BDBM50128264 (R,S)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionate CHEMBL72366 2-Amino-3-(4-chloro-3-hydroxy-isoxazol-5-yl)-propionic acid
BDBM50280705 CHEMBL15306 Sodium; (S)-3-{(R)-1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)-phenyl]-propylsulfanyl}-2-methyl-propionate
CHEMBL275357 Sodium; (R)-3-{(R)-1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)-phenyl]-propylsulfanyl}-2-methyl-propionate BDBM50280701
CHEMBL277533 BDBM50280706 Sodium; (R)-3-{(S)-1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)-phenyl]-propylsulfanyl}-2-methyl-propionate
Sodium; (S)-3-{(S)-1-[3-(7-chloro-quinolin-2-ylmethoxy)-phenyl]-3-[2-(1-hydroxy-1-methyl-ethyl)-phenyl]-propylsulfanyl}-2-methyl-propionate BDBM50280696 CHEMBL274913
Sodium; 2-{2-acetylamino-3,5-dihydroxy-6-[2-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-tetrahydro-pyran-4-yloxy}-3-phenyl-propionate CHEMBL336473 BDBM50096888
Sodium; 2-{2-carbamoyl-3,5-dihydroxy-6-[2-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-cyclohexyloxy]-tetrahydro-pyran-4-yloxy}-3-cyclohexyl-propionate CHEMBL140314 BDBM50096889
rac-(1R,2S)-2- (cyano(phenyl)(1-((1-(4- (pyridin-4- ylsulfonyl)phenyl)azetidin-3- yl)methyl)piperidin-4- yl)methylcyclopentyl propionate BDBM480136 US10899738, Cpd. No 196
Sodium; 3-[{3-[(E)-2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-(2-dimethylcarbamoyl-ethylsulfanyl)-methylsulfanyl]-propionate L-660771 BDBM50052019 Sodium;3-[{3-[(E)-2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-(2-dimethylcarbamoyl-ethylsulfanyl)-methylsulfanyl]-propionate CHEMBL89768 MK-571 sodium (E)-3-((3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)(3-(dimethylamino)-3-oxopropylthio)methylthio)propanoate
BDBM480135 US10899738, Cpd. No 195 rac-(1S,2R)-2- (cyano(phenyl)(1-((1-(4- (pyridin-4- ylsulfonyl)phenyl)azetidin-3- yl)methyl)piperidin-4- yl)methyl)cyclopentyl propionate
BDBM54704 cid_23681059 sodium;(2S)-2-(6-methoxynaphthalen-2-yl)propanoate UNM-0000306098 sodium;(2S)-2-(6-methoxy-2-naphthyl)propionate sodium;(2S)-2-(6-methoxy-2-naphthalenyl)propanoate
CHEMBL81732 BDBM50080294 Sodium; (S)-3-(1H-indol-3-yl)-2-[(S)-4-methyl-2-(3,4,5-trihydroxy-6-methyl-2-oxo-2lambda*5*-[1,2]oxaphosphinan-2-ylamino)-pentanoylamino]-propionate
cid_23675324 sodium;(2R)-2-(6-methoxy-2-naphthyl)propionate sodium;(2R)-2-(6-methoxynaphthalen-2-yl)propanoate BDBM54693 UNM-0000305812 sodium;(2R)-2-(6-methoxy-2-naphthalenyl)propanoate
propanoic acid [4-(2-quinoxalinyl)phenyl] ester (4-quinoxalin-2-ylphenyl) propanoate cid_768876 propionic acid (4-quinoxalin-2-ylphenyl) ester MLS000579684 4-(2-quinoxalinyl)phenyl propionate BDBM49530 SMR000186414
BDBM288124 US10087178, Example S65 7'-(3-chloro-2- fluorobenzylcarbamoyl)-cis- 3-methoxy-2'-methyl-1',8'- dioxo-1',2',3',8'- tetrahydrospiro[cyclobutane- 1,4'-pyrido[1,2-a]pyrazin]- 9'-yl propionate
BDBM50000561 CHEMBL290454 Sodium; 2-{2-[2-({2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoyl}-methyl-amino)-3-(1H-indol-3-yl)-propionylamino]-3-pyridin-2-yl-propionylamino}-3-phenyl-propionate
US10087178, Example S67 7'-(3-chloro-2- fluorobenzylcarbamoyl)-cis- 3-(methoxymethyl)-2'-methyl- 1',8'-dioxo-1',2',3',8'- tetrahydrospiro[cyclobutane- 1,4'-pyrido[1,2-a]pyrazin]- 9'-yl propionate BDBM288126
CHEMBL3215450 Sodium; (R)-3-cyclohexyl-2-{3,5-dihydroxy-2-hydroxymethyl-6-[2-hydroxymethyl-3-(3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-4-yloxy]-tetrahydro-pyran-4-yloxy}-propionate BDBM50098171
ethyl (S)-2-amino-3-(4- (4-((R)-1-(4-chloro-2- (3-methyl-1H-pyrazole- 1-yl)phenyl)-2,2,2- trifluoroethoxy)thieno [3,2-d]pyrimidine-7- yl)phenyl)propionate hydrochloride US11407763, Example 22 BDBM563490
Propionic acid (R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-4-methyl-pent-3-enyl ester (R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl propionate CHEMBL8951 BDBM50033725
sodium;3-[(4-methoxyphenyl)carbonylamino]-3-phenyl-propanoate KUC105717AM sodium;3-(p-anisoylamino)-3-phenyl-propionate BDBM61984 cid_23678497 sodium;3-[(4-methoxybenzoyl)amino]-3-phenylpropanoate sodium;3-[[(4-methoxyphenyl)-oxomethyl]amino]-3-phenylpropanoate KSC-09-176C
CHEMBL545608 4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl) 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one BDBM21398 Haloperidol CHEMBL54 Haloperidol, 1
3-[3-tert-Butylsulfanyl-1-(4-chloro-benzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid Sodium; 3-[3-tert-butylsulfanyl-1-(4-chloro-benzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionate MK-591 BDBM50052018 CHEMBL313489
propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate FENOFIBRATE Fenofibric acid CHEMBL672 Procetofen Finofibrate Lipantil (TN) 2-(4-(4-Chlorobenzoyl)phenoxy)-2-methylpropanoic acid 1-methylethyl ester BDBM50085042 Isopropyl (4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl)propionate Isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate Tricor (TN) FNF
azanium;2-(dodecanoylamino)-3-(4-methoxy-3-nitro-phenyl)propanoate BDBM90685 azanium;2-(dodecanoylamino)-3-(4-methoxy-3-nitrophenyl)propanoate cid_16682307 SMR000429460 2-Dodecanoylamino-3-(4-methoxy-3-nitro-phenyl)-propionic acid anion ammonium;3-(4-methoxy-3-nitrophenyl)-2-(1-oxododecylamino)propanoate ammonium;2-(lauroylamino)-3-(4-methoxy-3-nitro-phenyl)propionate MLS000767130
sodium;(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoate 3,3',5-TRIIODO-L-THYRONINE SODIUM SALT sodium;(2S)-2-amino-3-[4-(4-hydroxy-3-iodo-phenoxy)-3,5-diiodo-phenyl]propionate SMR000059206 sodium;(2S)-2-azanyl-3-[3,5-bis(iodanyl)-4-(3-iodanyl-4-oxidanyl-phenoxy)phenyl]propanoate BDBM50007 Triiodothyronine cid_23666110 MLS000028648
propionic acid 2-[[7-(1H-benzimidazol-2-ylthio)-4-nitro-benzofurazan-5-yl]amino]ethyl ester 2-[[7-(1H-benzimidazol-2-ylsulfanyl)-4-nitro-2,1,3-benzoxadiazol-5-yl]amino]ethyl propanoate BDBM33121 2-{[7-(1H-benzimidazol-2-ylthio)-4-nitro-2,1,3-benzoxadiazol-5-yl]amino}ethyl propionate MLS000584446 propanoic acid 2-[[7-(1H-benzimidazol-2-ylthio)-4-nitro-2,1,3-benzoxadiazol-5-yl]amino]ethyl ester SMR000207032 cid_12005314
2-[[7-(1-methylimidazol-2-yl)sulfanyl-4-nitro-2,1,3-benzoxadiazol-5-yl]amino]ethyl propanoate propanoic acid 2-[[7-[(1-methyl-2-imidazolyl)thio]-4-nitro-2,1,3-benzoxadiazol-5-yl]amino]ethyl ester BDBM33119 cid_12005273 MLS000584447 2-({7-[(1-methyl-1H-imidazol-2-yl)thio]-4-nitro-2,1,3-benzoxadiazol-5-yl}amino)ethyl propionate SMR000207033 propionic acid 2-[[7-[(1-methylimidazol-2-yl)thio]-4-nitro-benzofurazan-5-yl]amino]ethyl ester
MLS000550586 sodium;(2R)-2-[(2R,5S,6R)-6-[(3E,5E)-6-[(3aR,4S,5S,7aS)-4-(1H-pyrrole-2-carbonyl)-2,3,3a,4,5,7a-hexahydro-1H-inden-5-yl]hexa-3,5-dien-3-yl]-5-methyloxan-2-yl]propanoate sodium;(2R)-2-[(2R,5S,6R)-6-[(3E,5E)-6-[(3aR,4S,5S,7aS)-4-[oxo(1H-pyrrol-2-yl)methyl]-2,3,3a,4,5,7a-hexahydro-1H-inden-5-yl]hexa-3,5-dien-3-yl]-5-methyl-2-oxanyl]propanoate SMR000114418 sodium;(2R)-2-[(2R,5S,6R)-6-[(1E,3E)-4-[(3aR,4S,5S,7aS)-4-(1H-pyrrole-2-carbonyl)-2,3,3a,4,5,7a-hexahydro-1H-inden-5-yl]-1-ethyl-buta-1,3-dienyl]-5-methyl-tetrahydropyran-2-yl]propionate 2-(6-{1-ethyl-4-[4-(1H-pyrrol-2-ylcarbonyl)-2,3,3a,4,5,7a-hexahydro-1H-inden-5-yl]-1,3-butadienyl}-5-methyltetrahydro-2H-pyran-2-yl)propanoate cid_23670524 sodium;(2R)-2-[(2R,5S,6R)-6-[(3E,5E)-6-[(3aR,4S,5S,7aS)-4-(1H-pyrrol-2-ylcarbonyl)-2,3,3a,4,5,7a-hexahydro-1H-inden-5-yl]hexa-3,5-dien-3-yl]-5-methyl-oxan-2-yl]propanoate BDBM52222
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- Asami, T; Nishizawa, N; Matsui, H; Takatsu, Y; Suzuki, A; Kiba, A; Terada, M; Nishibori, K; Nakayama, M; Ban, J; Matsumoto, S; Tarui, N; Ikeda, Y; Yamaguchi, M; Kusaka, M; Ohtaki, T; Kitada, C Physicochemically and pharmacokinetically stable nonapeptide KISS1 receptor agonists with highly potent testosterone-suppressive activity. J Med Chem 57: 6105-15 (2014)
- Shimizu-Sasamata, M; Kawasaki-Yatsugi, S; Okada, M; Sakamoto, S; Yatsugi, S; Togami, J; Hatanaka, K; Ohmori, J; Koshiya, K; Usuda, S; Murase, K YM90K: pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist. J Pharmacol Exp Ther 276: 84-92 (1996)
- Marhefka, CA; Moore, BM; Bishop, TC; Kirkovsky, L; Mukherjee, A; Dalton, JT; Miller, DD Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands. J Med Chem 44: 1729-40 (2001)
- Ohmori, J; Kubota, H; Shimizu-Sasamata, M; Okada, M; Sakamoto, S Novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonists: synthesis and structure-activity relationships of 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione and related compounds. J Med Chem 39: 1331-8 (1996)
- Badorc, A; Bordes, MF; de Cointet, P; Savi, P; Bernat, A; Lalé, A; Petitou, M; Maffrand, JP; Herbert, JM New orally active non-peptide fibrinogen receptor (GpIIb-IIIa) antagonists: identification of ethyl 3-[N-[4-[4-[amino[(ethoxycarbonyl) imino]methyl]phenyl]-1,3-thiazol-2-yl]-N-[1-[(ethoxycarbonyl)methyl]pip erid -4-yl]amino]propionate (SR 121787) as a potent and long-acting antithrombotic agent. J Med Chem 40: 3393-401 (1997)
- ChEMBL_814102 (CHEMBL2020696) Reversible inhibition of CYP3A4-mediated conversion of testosterone to 6-beta-hydroxy-testosterone after 30 mins
- ChEBML_210239 Binding affinity towards testosterone receptor
- ChEMBL_51920 (CHEMBL663568) Inhibition of Cytochrome P450 3A4 with testosterone
- ChEMBL_581617 (CHEMBL1062504) Inhibition of CYP3A4 using testosterone as substrate
- ChEMBL_620426 (CHEMBL1112321) Inhibition of CYP3A4 using testosterone as a substrate
- ChEMBL_673953 (CHEMBL1275130) Inhibition of CYP3A4 using testosterone as substrate
- ChEMBL_701747 (CHEMBL1656750) Inhibition of CYP3A4 uisng testosterone substrate
- ChEMBL_792912 (CHEMBL1929758) Displacement of [3H]testosterone from AR
- ChEMBL_827974 (CHEMBL2051629) Inhibition of CYP3A4 using testosterone as substrate
- ChEMBL_858103 (CHEMBL2167215) Inhibition of CYP3A4 using testosterone as substrate
- ChEMBL_1772941 (CHEMBL4229933) Inhibition of human supersome CYP3A4 using testosterone as substrate assessed as testosterone 6beta-hydroxylation after 30 mins by HPLC-UV detection
- ChEMBL_1980041 (CHEMBL4613176) Inhibition of human CYP3A4 using testosterone as substrate
- ChEMBL_643970 (CHEMBL1211869) Inhibition of human CYP3A4-mediated testosterone oxidation
- ChEMBL_857030 (CHEMBL2162416) Reversible inhibition of CYP3A4 using testosterone as substrate
- ChEMBL_2291491 Inhibition of CYP3A4 in pooled human liver microsomes using testosterone as substrate assessed as reduction in 6-OH-testosterone metabolite formation by LC-MS/MS analysis
- ChEMBL_1432845 (CHEMBL3382683) Inhibition of CYP3A4 (unknown origin) using testosterone substrate
- ChEMBL_1435707 (CHEMBL3388340) Inhibition of CYP3A4 (unknown origin) using testosterone substrate
- ChEMBL_1442889 (CHEMBL3377702) Inhibition of CYP3A4 (unknown origin) using testosterone substrate
- ChEMBL_1513925 (CHEMBL3611607) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1613542 (CHEMBL3855342) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1696494 (CHEMBL4047384) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1780160 (CHEMBL4237152) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1794906 (CHEMBL4267023) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1855510 (CHEMBL4356239) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1865168 (CHEMBL4366143) Inhibition of human recombinant CYP3A4 using testosterone as substrate
- ChEMBL_1866304 (CHEMBL4367279) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1898402 (CHEMBL4400437) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1983162 (CHEMBL4616424) Inhibition of recombinant human CYP3A4 using testosterone as substrate
- ChEMBL_1983163 (CHEMBL4616425) Inhibition of recombinant human CYP3A5 using testosterone as substrate
- ChEMBL_1983174 (CHEMBL4616436) Inhibition of recombinant human CYP3A4 using testosterone as substrate
- ChEMBL_1983175 (CHEMBL4616437) Inhibition of recombinant human CYP3A5 using testosterone as substrate
- ChEMBL_1983186 (CHEMBL4616448) Inhibition of recombinant human CYP3A4 using testosterone as substrate
- ChEMBL_1983187 (CHEMBL4616449) Inhibition of recombinant human CYP3A5 using testosterone as substrate
- ChEMBL_2020183 (CHEMBL4673996) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2024275 (CHEMBL4678088) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2115923 (CHEMBL4824864) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2148408 (CHEMBL5032806) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2156398 (CHEMBL5041058) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2186328 (CHEMBL5098410) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2233885 (CHEMBL5147657) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2240170 (CHEMBL5154066) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_50540 (CHEMBL661157) Inhibition of human placental cytochrome P450 19A1 with testosterone
- ChEMBL_51034 (CHEMBL662247) Inhibition of human placental cytochrome P450 19A1 with testosterone
- ChEMBL_51036 (CHEMBL662249) Inhibition of human placental cytochrome P450 19A1 with testosterone
- ChEMBL_741042 (CHEMBL1764270) Inhibition of human CYP3A4 in human liver microsomes assessed as formation of 6beta-hydroxy-testosterone using testosterone as substrate by high throughput mass spectrometry in absence of NADPH
- ChEMBL_1468060 (CHEMBL3413698) Inhibition of CYP3A4 (unknown origin) using testosterone as marker substrate
- ChEMBL_1589887 (CHEMBL3830767) Inhibition of human placental microsomal aromatase using testosterone as substrate
- ChEMBL_1667019 (CHEMBL4016815) Inhibition of human liver microsomes CYP3A4 using testosterone as substrate
- ChEMBL_1748557 (CHEMBL4183067) Inhibition of CYP3A4-mediated testosterone metabolism in human liver microsomes
- ChEMBL_1817350 (CHEMBL4317010) Reversible inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_1896396 (CHEMBL4398431) Inhibition of human aromatase using [1beta,2beta3H]-]testosterone as substrate
- ChEMBL_1914413 (CHEMBL4416996) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_1935816 (CHEMBL4481575) Time-dependent inhibition of human CYP3A4 using testosterone as substrate
- ChEMBL_2056542 (CHEMBL4711543) Inhibition of CYP3A4 in human liver microsome using testosterone as substrate
- ChEMBL_2125914 (CHEMBL4835259) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_2151594 (CHEMBL5036056) Inhibition of CYP3A4 in human liver microsome using testosterone as substrate
- ChEMBL_2165881 (CHEMBL5050742) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_2216951 (CHEMBL5130083) Inhibition of CYP3A4 in human liver microsome using testosterone as substrate
- ChEMBL_2232925 (CHEMBL5146697) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_2253951 (CHEMBL5168161) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_813719 (CHEMBL2019921) Inhibition of CYP3A4 in human liver microsomes co-incubated with testosterone
- ChEMBL_875802 (CHEMBL2186748) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_741043 (CHEMBL1764271) Inhibition of human CYP3A4 in human liver microsomes assessed as formation of 6beta-hydroxy-testosterone using testosterone as substrate by high throughput mass spectrometry preincubated for 30 mins in presence of NADPH
- ChEBML_1683160 Inhibition of CYP3A4 in human liver microsomes using testosterone, midozolam or nifedipine as substrates
- ChEMBL_1283600 (CHEMBL3107752) Inhibition of CYP3A4 in human liver microsomes assessed as 6beta-hydroxylation of testosterone
- ChEMBL_1462161 (CHEMBL3396935) Reversible inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_1554473 (CHEMBL3767770) Inhibition of CYP3A4 in human liver microsomes assessed as testosterone 6beta-hydroxylation
- ChEMBL_1747252 (CHEMBL4181762) Inhibition of human CYP3A4 using testosterone as substrate preincubated for 30 mins
- ChEMBL_1817351 (CHEMBL4317011) Time dependent inhibition of CYP3A4 (unknown origin) using testosterone as substrate
- ChEMBL_2100795 (CHEMBL4809191) Direct inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
- ChEMBL_2100796 (CHEMBL4809192) Direct inhibition of CYP3A5 in human liver microsomes using testosterone as substrate
- ChEMBL_210247 (CHEMBL883487) Binding constant of Testosterone-5 alpha-reductase activity at pH 7.4
- ChEMBL_2221809 (CHEMBL5135143) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate in presence of NADPH
- ChEMBL_2221810 (CHEMBL5135144) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate pretreated with NADPH
- ChEMBL_320884 (CHEMBL884809) Binding affinity to androgen receptor by incubation with GST-hARLBD and [3H]testosterone
- ChEMBL_487546 (CHEMBL1013140) Displacement of [3H]testosterone from wild type human androgen receptor
- ChEMBL_753596 (CHEMBL1799313) Reversible inhibition of CYP3A4 assessed as conversion of testosterone to 6-beta-hydroxytestosterone
- ChEMBL_859942 (CHEMBL2167345) Inhibition of human CYP3A4 using testosterone as substrate after 45 mins
- ChEMBL_1362982 (CHEMBL3292550) Inhibition of CYP3A4 in human liver microsomes assessed as testosterone conversion to 6-hydroxy testosterone preincubated for 10 mins followed by NADPH addition measured after 15 mins by LC-MS/MS analysis
- ChEMBL_1625607 (CHEMBL3868076) Inhibition of human Cyp3A4 using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_1713962 (CHEMBL4124011) Inhibition of human CYP3A4 using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_210244 (CHEMBL809272) Inhibition of Testosterone-5 alpha-reductase activity at pH 7.4 from rat
- ChEMBL_2125132 (CHEMBL4834365) Inhibition of human CYP3A4 using testosterone as a substrate by LC/MS/MS analysis
- ChEMBL_2157118 (CHEMBL5041778) Inhibition of human CYP3A4 using testosterone as substrate by fluorescence plate reader analysis
- ChEMBL_2240607 (CHEMBL5154503) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH
- ChEMBL_225417 (CHEMBL847453) In vitro inhibitory activity against rat testosterone 5 alpha reductase was determined
- ChEMBL_2265894 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS analysis
- ChEMBL_738395 (CHEMBL1743472) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone hydroxylation
- ChEMBL_738408 (CHEMBL1743485) Mechanism based inhibition of human cytochrome P450 3A5 measured by testosterone hydroxylation
- ChEMBL_753598 (CHEMBL1799315) Time dependent inhibition of CYP3A4 assessed as conversion of testosterone to 6-beta-hydroxytestosterone
- ChEMBL_813040 (CHEMBL2020552) Inhibition of human CYP3A4 using testosterone as substrate by LC/MS/MS analysis
- ChEBML_50700 Inhibition of cytochrome P450 19A1 of human placental microsomes with [1-beta,2beta-3H]testosterone
- ChEMBL_1447575 (CHEMBL3373770) Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPLC/MS/MS method
- ChEMBL_1539997 (CHEMBL3737755) Inhibition of rat liver type 1 5alpha-reductase assessed as transformation of testosterone to dihydrotestosterone
- ChEMBL_1539998 (CHEMBL3737756) Inhibition of human prostate type 2 5alpha-reductase assessed as transformation of testosterone to dihydrotestosterone
- ChEMBL_1584554 (CHEMBL3820545) Inhibition of human aromatase using testosterone as substrate incubated for 1 hr by HTRF assay
- ChEMBL_1618865 (CHEMBL3861034) Inhibition of CYP3A4 in pooled human hepatic microsomes using testosterone substrate in presence of NADPH
- ChEMBL_210241 (CHEMBL809269) Inhibition of rat testosterone-5 alpha-reductase activity at pH 6.6 from rat
- ChEMBL_2165351 (CHEMBL5050212) Inhibition of recombinant human CYP3A4 using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_2252754 (CHEMBL5166964) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence or absence of NADPH
- ChEMBL_50691 (CHEMBL663078) Inhibition of Cytochrome P450 19A1 against testosterone at 1.5 uM (Km=0.13 uM)
- ChEMBL_51017 (CHEMBL664409) Inhibition of Cytochrome P450 19A1 against testosterone at 1.5 uM (Km=0.13 uM)
- ChEMBL_572594 (CHEMBL1025210) Inhibition of CYP3A4 in human liver microsomes assessed as inhibition of testosterone 6-beta-hydroxylation
- ChEMBL_726892 (CHEMBL1686598) Displacement of [3H]testosterone from Sprague-Dawley rat AR by liquid scintillation counting
- ChEMBL_738394 (CHEMBL1743471) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone beta-hydroxylation
- ChEMBL_821319 (CHEMBL2040149) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by fluorescence detection assay
- ChEMBL_942984 (CHEMBL2343820) Inhibition of CYP3A4/5 in human liver microsomes assessed as reduction in testosterone-beta-hydroxylation
- ChEMBL_1491569 (CHEMBL3535031) Inhibition of human recombinant CYP3A5 using testosterone as substrate assessed as testosterone 6-beta-hydroxylation preincubated up to 30 mins with NADPH followed by substrate addition measured after 10 mins by LC/MS/MS analysis
- ChEMBL_2241392 (CHEMBL5155602) Inhibition of CYP3A4 in human liver microsomes assessed as reduction in 6-beta-hydroxy-testosterone formation using testosterone as substrate preincubated for 20 mins in presence of NADPH followed by incubation with substrate for 10 mins by LC-MS/MS analysis
- ChEMBL_2241412 (CHEMBL5155622) Inhibition of CYP3A4 in human liver microsomes assessed as reduction in 6-beta-hydroxy-testosterone formation using testosterone as substrate preincubated for 20 mins in absence of NADPH followed by incubation with substrate for 10 mins by LC-MS/MS analysis
- ChEBML_36132 Dissociation constant against GST-hARLBD was measured in SC-3 cell by using [3H]testosterone as radioligand
- ChEMBL_1347924 (CHEMBL3267461) Inhibition of human hepatocyte microsome CYP3A4 using testosterone as substrate by HPLC/MS/MS method
- ChEMBL_1441437 (CHEMBL3373392) Inhibition of rat liver 5alpha-reductase type 1 assessed as conversion of [3H]testosterone to dihydrotestosterone
- ChEMBL_1441438 (CHEMBL3373987) Inhibition of human prostate 5alpha-reductase type 2 assessed as conversion of [3H]testosterone to dihydrotestosterone
- ChEMBL_1485703 (CHEMBL3541095) Inhibition of CYP3A4 in human liver microsomes using testosterone substrate by LC-MS/MS method
- ChEMBL_1492827 (CHEMBL3527957) Inhibition of CYP3A4 activity in human liver microsomes using testosterone as a substrate by LC/MS analysis
- ChEMBL_1520473 (CHEMBL3624602) Inhibition of human placental aromatase in presence of [1beta,2beta-3H] testosterone by Thompson and Siiteri method
- ChEMBL_1653831 (CHEMBL4003197) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by HPLC-MS/MS method
- ChEMBL_1705360 (CHEMBL4056593) Inhibition of CYP3A4 in human hepatocyte microsomes using testosterone substrate by HPLC/MS/MS method
- ChEMBL_1705370 (CHEMBL4056603) Inhibition of CYP19 in human hepatocyte microsomes using testosterone substrate by HPLC/MS/MS method
- ChEMBL_1979603 (CHEMBL4612738) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_2051671 (CHEMBL4706370) Inhibition of CYP3A4 in human liver microsomes using testosterone substrate by LC-MS/MS analysis
- ChEMBL_2062192 (CHEMBL4717445) Inhibition of human liver microsomes CYP3A4 using testosterone as substrate by MUX-MS/MS analysis
- ChEMBL_2110160 (CHEMBL4818835) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_2149012 (CHEMBL5033410) Inhibition of human CYP3A4 using testosterone as substrate in presence of NADPH incubated for 15 to 45 mins
- ChEMBL_2157126 (CHEMBL5041786) Time dependent inhibition of human CYP3A4 using testosterone as substrate by fluorescence plate reader analysis
- ChEMBL_2187311 (CHEMBL5099393) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by HPLC analysis
- ChEMBL_2214899 (CHEMBL5128031) Inhibition of CYP3A4 in human hepatocyte microsomes using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_2272999 Inhibition of CYP3A4 in human liver microsomes using midazolam/testosterone as substrate by LC-MS/MS analysis
- ChEMBL_322421 (CHEMBL873543) Androgen antagonistic activity as inhibitory concentration against testosterone-induced SC-3 cell proliferation
- ChEMBL_327080 (CHEMBL859578) Displacement of [3H]-[1-beta,2beta]-testosterone from 5alpha reductase2 in human prostrate homogenate
- ChEMBL_50552 (CHEMBL660330) Inhibition of human Placental Cytochrome P450 19A1 in vitro using human placental microsomes and testosterone
- ChEMBL_738373 (CHEMBL1743450) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738375 (CHEMBL1743452) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738376 (CHEMBL1743453) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738377 (CHEMBL1743454) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738379 (CHEMBL1743456) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738380 (CHEMBL1743457) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738381 (CHEMBL1743458) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738383 (CHEMBL1743460) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738384 (CHEMBL1743461) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738385 (CHEMBL1743462) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738388 (CHEMBL1743465) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_738389 (CHEMBL1743466) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation
- ChEMBL_817424 (CHEMBL2027647) Inhibition of CYP3A4 using testosterone as substrate in human liver microsome for 20 mins by HPLC analysis
- ChEMBL_821298 (CHEMBL2040128) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_854487 (CHEMBL2160809) Inhibition of human CYP3A4 in liver microsomes assessed as testosterone 6beta-hydroxylation after 48 hrs
- ChEMBL_873340 (CHEMBL2185193) Time dependent inhibition of CYP3A4-mediated testosterone-6-beta hydroxylation in human liver microsome
- ChEMBL_940630 (CHEMBL2327572) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS-MS analysis
- ChEMBL_1655304 (CHEMBL4004670) Inhibition of CYP3A4 using in human liver microsomes using testosterone as substrate after 5 to 15 mins
- ChEMBL_1667020 (CHEMBL4016816) Inhibition of human liver microsomes CYP3A4 using testosterone as substrate preincubated with compound followed by substrate addition
- ChEMBL_2100805 (CHEMBL4809201) Time-dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 30 mins
- ChEMBL_2100806 (CHEMBL4809202) Time-dependent inhibition of CYP3A5 in human liver microsomes using testosterone as substrate preincubated for 30 mins
- ChEMBL_2216964 (CHEMBL5130096) Time dependent inhibition of CYP3A4 in human liver microsome using testosterone as substrate preincubated for 30 mins
- ChEMBL_2262777 (CHEMBL5217788) Inhibition of CYP3A4 in human liver microsomes using midazolam and testosterone as substrate in presence NADPH regenerating system
- ChEMBL_2296122 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_36057 (CHEMBL645588) In vitro inhibitory concentration against Aromatase was determined using [1-beta,2beta-3H]testosterone as radioligand
- ChEMBL_36135 (CHEMBL648324) Binding affinity against GST-hARLBD was measured in SC-3 cell by using [3H]testosterone as radioligand
- ChEMBL_738411 (CHEMBL1743488) Mechanism based inhibition of rabbit cytochrome P450 3A6 measured by testosterone and progesterone 6-beta hydroxylation
- ChEMBL_753597 (CHEMBL1799314) Time dependent inhibition of CYP3A4 assessed as conversion of testosterone to 6-beta-hydroxytestosterone preincubated for 30 mins
- ChEMBL_850907 (CHEMBL2156890) Inhibition of human CYP3A4 using testosterone as substrate after 15 mins by LC/MS/MS analysis
- ChEMBL_1458157 (CHEMBL3368203) Inhibition of human CYP3A4 using testosterone as substrate after 10 mins by SPE-MS analysis in presence of NADPH
- ChEMBL_1487665 (CHEMBL3532651) Reversible inhibition of testosterone 6beta-hydroxylase activity of human recombinant CYP3A4 in presence of human P450 oxidoreductase and b5
- ChEMBL_1487667 (CHEMBL3532653) Reversible inhibition of testosterone 6beta-hydroxylase activity of human recombinant CYP3A5 in presence of human P450 oxidoreductase and b5
- ChEMBL_1497736 (CHEMBL3582742) Inhibition of human recombinant CYP3A4 using testosterone as substrate after 1 hr by LC-MS/MS analysis
- ChEMBL_1512777 (CHEMBL3611370) Inhibition of CYP3A4 in human liver microsomes assessed as reduction in testosterone 6beta-hydroxylation by LC-MS/MS method
- ChEMBL_1584556 (CHEMBL3820547) Inhibition of human placental microsomal aromatase using testosterone as substrate assessed as formation of estradiol after 10 mins
- ChEMBL_1584799 (CHEMBL3821882) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 5 mins by LC-MS analysis
- ChEMBL_1624780 (CHEMBL3867192) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1627005 (CHEMBL3869526) Antagonist activity at androgen receptor in human MDA-MB-453 cells assessed as inhibition of testosterone-induced transactivation
- ChEMBL_1653051 (CHEMBL4002306) Inhibition of human prostate 5-alpha reductase 2 assessed as decrease in conversion of testosterone to dihydrotestosterone by chromatographic method
- ChEMBL_1659464 (CHEMBL4009076) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1712694 (CHEMBL4122743) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1912369 (CHEMBL4414952) Inhibition of CYP3A4 in human liver microsomes at 1 uM using testosterone as substrate by LC-MS/MS analysis
- ChEMBL_1923418 (CHEMBL4426374) Inhibition of human CYP3A4 expressed in supersomes assessed as testosterone 6beta-hydroxylation after 15 mins by HPLC analysis
- ChEMBL_2226861 (CHEMBL5140374) Inhibition of CYP3A4T in human liver microsomes using testosterone as substrate incubated for 15 to 40 mins in presence of NADPH
- ChEMBL_2246147 (CHEMBL5160357) Inhibition of human liver CYP3A4 expressed in baculovirus-infected insect cell supersomes assessed as testosterone 6-hydroxylation
- ChEMBL_609086 (CHEMBL1066534) Inhibition of CYP3A4-mediated hydroxylation of testosterone in human liver microsomes in NADPH co-factor system by RP-HPLC
- ChEMBL_699332 (CHEMBL1647250) Inhibition of human prostate 5alpha-reductase type 2 assessed as formation dihydrotestosterone from [4-14C] testosterone
- ChEMBL_790052 (CHEMBL1926384) Inhibition of recombinant human CYP3A4 assessed as conversion of testosterone into 6-hydroxytestosterone after 30 mins by HPLC analysis
- ChEMBL_796573 (CHEMBL1937888) Inhibition of human 17beta-HSD3 expressed in HeLa cells assessed as conversion of 4-androstene-3,17-dione to testosterone
- ChEMBL_977682 (CHEMBL2423840) Displacement of [3H]-Testosterone from human AR expressed in 293 cells after 16 hrs by scintillation counting
- ChEMBL_862370 (CHEMBL2173314) Inhibition of NHE1 in rat platelet rich plasma assessed as reduction of propionate medium induced platelet swelling measured every 6 secs for 5 mins
- ChEMBL_862404 (CHEMBL2173434) Inhibition of NHE1 in human platelet rich plasma assessed as reduction of propionate medium induced platelet swelling measured every 6 secs for 5 mins
- ChEBML_204741 Inhibitory activity against human 5-alpha-reductase type 2 using 18213 3H testosterone 210 nM as substrate
- ChEMBL_1366898 (CHEMBL3297539) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 15 mins by LC/MS/MS analysis
- ChEMBL_1445200 (CHEMBL3375452) Inhibition of human CYP3A4 testosterone site in human liver microsomes using midazolam as substrate by LC-MS/MS analysis
- ChEMBL_1496402 (CHEMBL3580168) Inhibition of CYP3A4 in human liver microsomes using testosterone substrate incubated for 30 mins by LC-MS/MS method
- ChEMBL_1578569 (CHEMBL3811610) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 10 mins by LC/MS/MS analysis
- ChEMBL_1616181 (CHEMBL3858250) Inhibition of CYP3A4 in human liver microsomes using testosterone/midazolam as substrate in presence of NADPH by LC/MS/MS analysis
- ChEMBL_1624792 (CHEMBL3867204) Reversible inhibition of CYP3A4 in human liver microsomes using testosterone as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_2035475 (CHEMBL4689633) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 30 mins by LC-MS/MS analysis
- ChEMBL_2046450 (CHEMBL4701149) Time-dependent inhibition of CYP3A4 in human liver microsomes using testosterone in presence of NADPH by LC-MS/MS analysis
- ChEMBL_2066474 (CHEMBL4721727) Inhibition of human liver microsome CYP3A4 using testosterone as substrate incubated for 20 mins by LC-MS/MS analysis
- ChEMBL_2109895 (CHEMBL4818570) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 10 mins by LC/MS/MS analysis
- ChEMBL_2157144 (CHEMBL5041804) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by TDI- high-throughput based mass spectrometry method
- ChEMBL_2158993 (CHEMBL5043743) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 30 mins by LC-MS/MS analysis
- ChEMBL_738390 (CHEMBL1743467) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation and erythromycin N-demethylation
- ChEMBL_738393 (CHEMBL1743470) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation using a recombinant system
- ChEMBL_790073 (CHEMBL1925463) Inhibition of human B-lymphoblastoid cell microsomal CYP3A4 assessed as testosterone 6beta-hydroxylation preincubated for 5 mins with substrate
- ChEBML_204888 Inhibitory activity against rat Steroid 5-alpha-reductase type I using 18213 3H testosterone 210 nM as substrate
- ChEBML_50537 In vitro inhibitory concentration against human placental Cytochrome P450 19A was determined using [1-beta,2beta-3H]testosterone as radioligand
- ChEMBL_1438887 (CHEMBL3381812) Displacement of [3H]testosterone from androgen receptor (unknown origin) expressed in 293 cells after 16 hrs by scintillation counting
- ChEMBL_1487045 (CHEMBL3531871) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 5 to 30 mins by LC-MS/MS analysis
- ChEMBL_1578010 (CHEMBL3806759) Inhibition of CYP3A4 in human liver microsomes using testosterone/midazolam as substrate after 30 mins by LC/MS/MS analysis
- ChEMBL_1619558 (CHEMBL3861727) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 10 mins in presence of NADP by rapidfire/MS analysis
- ChEMBL_1785086 (CHEMBL4256603) Inhibition of CYP3A4 in human liver microsomes using testosterone/midazolam as substrate after 30 mins by LC-MS/MS method
- ChEMBL_1803976 (CHEMBL4276268) Inhibition of CYP3A4 in human liver microsomes using midazolam/testosterone as substrate after 10 to 30 mins by LC/MS analysis
- ChEMBL_1973582 (CHEMBL4606400) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate measured after 15 mins by LC-MS/MS analysis
- ChEMBL_2073306 (CHEMBL4728840) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate measured after 15 mins by LC-MS/MS analysis
- ChEMBL_2101777 (CHEMBL4810173) Inhibition of CYP3A4 in human liver microsomes using midazolam or testosterone as substrate substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_2150741 (CHEMBL5035203) Inhibition of CYP3A4 in human pooled liver microsomes using midazolam and testosterone as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_50701 (CHEMBL661695) In vitro inhibition of cytochrome P450 19A1 from human placental microsomes with 2.5 uM [1-beta,2beta-3H]testosterone
- ChEMBL_738392 (CHEMBL1743469) Mechanism based inhibition of human cytochrome P450 3A4 measured by testosterone 6-beta hydroxylation using human liver microsomes
- ChEMBL_975807 (CHEMBL2415373) Inhibition of human 17beta-HSD5 expressed in HEK293 cells using androstenedione as substrate assessed as testosterone synthesis after 4 hrs
- Scintillation Proximity Assay (SPA) SPA beads conjugated to anti-mouse IgG were incubated overnight in buffer with anti-testosterone monoclonal antibody. The enzymatic reaction was monitored by its conversion of 4-androstene-3, 17-dione to testosterone. The amount of [14C] testosterone produced in each well was determined by scintillation counting on a Perkin Elmer TopCount instrument and collected as DPMs. The data was then analyzed and percent inhibition and/or IC50 values, based on 10 point serially diluted curves in duplicate or triplicate, were calculated using Microsoft Excel and XLFit programs.
- ChEBML_306524 Inhibition of [1-beta-2beta-3H]- -testosterone binding to human steroid 5-alpha-reductase type 2 of BPH tissue at 10 uM
- ChEMBL_1713508 (CHEMBL4123557) Inhibition of CYP3A4 in human liver microsomes assessed as testosterone 6beta-hydroxylation after 4 to 40 mins in presence of NADPH by LCMS analysis
- ChEMBL_1869499 (CHEMBL4370565) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 10 mins in presence of NADP by LC-MS/MS analysis
- ChEMBL_1992483 (CHEMBL4626218) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 10 mins in presence of NADPH by LC/MS/MS analysis
- ChEMBL_2022078 (CHEMBL4675891) Time-dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate and in presence of co-factor by LC-MS/MS analysis
- ChEMBL_204742 (CHEMBL805435) Inhibitory activity against human Steroid 5-alpha-reductase type 2 using 18213 3H testosterone 210 nM as substrate
- ChEMBL_2075863 (CHEMBL4731397) Inhibition of CYP3A4 in human pooled liver microsomes using testosterone as substrate measured up to 20 mins by UHPLC-MS/MS analysis
- ChEMBL_2188254 (CHEMBL5100336) Inhibition of human liver microsomes CYP3A4 using midazolam or testosterone as substrate in presence of NADPH regenerating system by LC-MS/MS analysis
- ChEMBL_2278329 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 10 to 30 mins in presence of NADPH by LC-MS/MS method
- ChEMBL_2280218 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate measured after 15 mins in the presence of NADPH by LC/MS/MS analysis
- ChEMBL_50537 (CHEMBL661154) In vitro inhibitory concentration against human placental Cytochrome P450 19A was determined using [1-beta,2beta-3H]testosterone as radioligand
- ChEMBL_775988 (CHEMBL1912986) Displacement of [3H]testosterone from androgen receptor in Sprague-Dawley rat prostate gland after 2 hrs by liquid scintillation counting
- ChEMBL_975806 (CHEMBL2415372) Inhibition of human 17beta-HSD5 expressed in human CWR22R cells using androstenedione as substrate assessed as testosterone synthesis after 4 hrs
- ChEBML_1653456 Inhibition of platelet NHE1 in human platelet rich plasma assessed as decrease in platelet swelling preincubated for 3 mins followed by sodium propionate addition measured after 4 mins by spectrophotometric method
- ChEMBL_1492470 (CHEMBL3528845) Inhibition of CYP3A4 in human liver microsomes assessed as testosterone 6beta-hydroxylation after 3 mins by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1492480 (CHEMBL3528855) Inhibition of CYP3A4 in human liver microsomes assessed as testosterone 6beta-hydroxylation preincubated for 15 mins by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1520476 (CHEMBL3624715) Inhibition of human placental aromatase assessed as conversion of 3H2O from [1beta,2beta-3H] testosterone after 20 mins by scintillation spectrometer analysis
- ChEMBL_1658362 (CHEMBL4007974) Inhibition of microsomal CYP3A4 (unknown origin) using testosterone as substrate preincubated for 5 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_1661010 (CHEMBL4010622) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition measured after 10 mins
- ChEMBL_1667937 (CHEMBL4017825) Inhibition of CYP3A4 in human liver microsomes using midazolam/testosterone as substrate after 30 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1797911 (CHEMBL4270028) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate after 30 mins in presence of NADPH measured by LC-MS/MS analysis
- ChEMBL_1859913 (CHEMBL4360769) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate measured after 10 mins in presence of NADPH by UHPLC-MS/MS analysis
- ChEMBL_2022781 (CHEMBL4676594) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate measured after 5 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_2046448 (CHEMBL4701147) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate measured after 15 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_204910 (CHEMBL809545) Evaluated for the inhibitory activity against human steroid 5-alpha-reductase type 2 from human BPH tissue at 210 nM of testosterone
- ChEMBL_2100086 (CHEMBL4808482) Inhibition of CYP3A4 in human liver microsomes assessed as reduction in testosterone 6beta-hydroxylation activity by high-pressure liquid chromatography-tandem mass spectrometry
- ChEMBL_2101739 (CHEMBL4810135) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_2188216 (CHEMBL5100298) Inhibition of CYP3A4 (unknown origin) in microsomes sing testosterone as a substrate preincubated for 5 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_2253558 (CHEMBL5167768) Inhibition of CYP3A4 in human liver microsomes using midazolam and testosterone as substrate incubated for 5 to 45 mins in presence of NADPH by LC/MS analysis
- ChEMBL_2277116 Inhibition of CYP3A4 (unknown origin) using testosterone as substrate incubated for 10 to 20 mins in presence of NADPH-generating system by LC-MS/MS analysis
- ChEMBL_675520 (CHEMBL1273733) Antiandrogen activity against androgen receptor in androgen-dependent mouse SC3 cells assessed as inhibition of testosterone-induced cell proliferation by WST1 assay
- ChEMBL_900593 (CHEMBL3062621) Inhibition of Homo sapiens (human) aromatase assessed as 3H2O formation using [1beta,2beta-3H]testosterone as substrate by liquid scintillation counting analysis
- ChEMBL_942992 (CHEMBL2343828) Antagonist activity at androgen receptor in androgen-dependent mouse SC3 cells assessed as inhibition of testosterone-induced cell growth after 3 days
- ChEMBL_1653456 (CHEMBL4002822) Inhibition of platelet NHE1 in human platelet rich plasma assessed as decrease in platelet swelling preincubated for 3 mins followed by sodium propionate addition measured after 4 mins by spectrophotometric method
- ChEMBL_1449353 (CHEMBL3372081) Inhibition of Sprague-Dawley rat liver steroid 5-alpha-reductase assessed as inhibition of testosterone conversion to dihydrotestosterone incubated for 30 mins by HPLC method
- ChEMBL_1574682 (CHEMBL3801549) Inhibition of CYP3A4 in human liver microsomes using testosterone and midazolam as substrate preincubated for 30 mins followed substrate addition by LC-MS/MS analysis
- ChEMBL_1673854 (CHEMBL4023883) Inhibition of CYP3A4 in human liver microsomes assessed as decrease in formation of 6beta-hydroxytestosterone from testosterone after 10 mins by LC-MS/MS analysis
- ChEMBL_1701329 (CHEMBL4052311) Inhibition of CYP3A4 in human liver microsomes assessed as decrease in formation of 6beta-hydroxytestosterone from testosterone after 10 mins by LC-MS/MS analysis
- ChEMBL_2118301 (CHEMBL4827367) Reversible inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition by LC/MS/MS analysis
- ChEMBL_775863 (CHEMBL1912404) Inhibition of CYP3A4 in human liver microsomes assessed as inhibition of oxidative metabolism of testosterone after 45 mins by MS analysis in the presence of 1 mmol NADPH
- ChEMBL_1491683 (CHEMBL3536516) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by substrate addition by LC-MS/MS analysis
- ChEMBL_1491685 (CHEMBL3536518) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 90 mins followed by substrate addition by LC-MS/MS analysis
- ChEMBL_1492496 (CHEMBL3529079) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate assessed as residual enzyme activity after 2 to 10 mins by LC-MS/MS analysis
- ChEMBL_1575837 (CHEMBL3801880) Inhibition of 17betaHSD3 (unknown origin) transfected in human LNCAP cells assessed as conversion of [14C]-4-androstene-3,17-dione into [14C]-testosterone after 3 hrs
- ChEMBL_1614025 (CHEMBL3855825) Inhibition of CYP3A4 in human liver microsomes assessed as 6-beta-hydroxytestosterone metabolite formation using testosterone as substrate incubated for 30 mins by HPLC-MS method
- ChEMBL_1677535 (CHEMBL4027678) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate upto 10 uM after 5 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1896395 (CHEMBL4398430) Inhibition of human placental microsome aromatase using [1beta,2beta3H]-]testosterone as substrate measured up to 21 mins in presence of NADPH by liquid scintillation spectrometer method
- ChEMBL_1972623 (CHEMBL4605441) Inhibition of CYP3A4/5 in human liver microsomes using testosterone as substrate measured for 10 to 30 mins in presence of NADPH regenerating system by UPLC-MS analysis
- ChEMBL_2124316 (CHEMBL4833549) Inhibition of CYP3A4 in human liver microsomes assessed as testosterone 6-beta-hydroxylation reaction incubated for 30 mins in presence of NADP by LC-MS/MS analysis
- ChEMBL_2237251 (CHEMBL5151147) Time dependent inhibition of human liver microsome CYP3A4 preincubated for 0.5 hrs in presence or absence of NADPH followed by testosterone addition by LC-MS/MS method
- ChEMBL_1462490 (CHEMBL3398963) Inhibition of CYP3A4 in pooled mixed-gender human liver microsomes using testosterone substrate in presence of NADPH pre-incubated for 3 mins by HPLC-UV detection method
- ChEMBL_159371 (CHEMBL768145) Binding affinity against Progesterone receptor in human TE85 osteosarcoma cells was determined using (Z)-[125I]-17-alpha-(2-iodovinyl)-19-nor-testosterone as radioligand
- ChEMBL_1764609 (CHEMBL4199856) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate pretreated for 5 mins followed by NADPH addition and measured after 5 mins by LC-MS analysis
- ChEMBL_1817314 (CHEMBL4316974) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition and measured for 15 mins by LC-MS/MS analysis
- ChEMBL_2016125 (CHEMBL4669703) Inhibition of CYP3A4 (unknown origin) using testosterone as substrate preincubated for 5 mins followed by addition of NADPH measured after 20 mins by LC-MS/MS analysis
- ChEMBL_225213 (CHEMBL841571) Inhibitory concentration against human recombinant steroid 5-alpha-reductase type 2 in stably transfected chinese hamster ovary 1827 cells using [3H]testosterone
- ChEMBL_2273354 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
- ChEMBL_487550 (CHEMBL1013144) Antagonist activity at wild type human recombinant androgen receptor assessed as inhibition of testosterone-induced growth of mouse androgen dependent SC3 cells by WST-1 method
- ChEMBL_565719 (CHEMBL962458) Inhibition of human 17beta-HSD5 expressed in HEK293 cells assessed as enzyme-mediated transformation of [14C]-4-androstene-3,17-dione in to [14C]-testosterone after 18 hrs
- ChEMBL_823391 (CHEMBL2046050) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 3 mins prior to NAPDH-addition measured after 30 mins by RP-HPLC analysis
- ChEMBL_1491687 (CHEMBL3536520) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by substrate addition by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1491689 (CHEMBL3536522) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 90 mins followed by substrate addition by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1688700 (CHEMBL4039270) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 15 mins measured after 8 mins in presence or absence of NADPH by LC/MS/MS analysis
- ChEMBL_1849385 (CHEMBL4349926) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
- ChEMBL_1902240 (CHEMBL4404462) Inhibition of CYP3A in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
- ChEMBL_1902876 (CHEMBL4405098) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
- ChEMBL_2022083 (CHEMBL4675896) Inhibition of human CYP3A4 in human liver microsomes using testosterone as substrate and in presence of co-factor preincubated for 20 mins followed by substrate addition by LC-MS/MS analysis
- ChEMBL_205065 (CHEMBL810259) Inhibitory concentration against human recombinant steroid 5-alpha-reductase type I in stably transfected chinese hamster ovary (CHO) 1827 cells using [3H]testosterone.
- ChEMBL_2091855 (CHEMBL4773118) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH addition and measured after 5 mins by LC-MS/MS analysis
- ChEMBL_2093986 (CHEMBL4775249) Inhibition of human CYP3A4 in human pooled liver microsomes in presence of testosterone as substrate preincubated for 0 mins in presence of NADPH followed by addition of substrate by LC-MS/MS analysis
- ChEMBL_2093988 (CHEMBL4775251) Inhibition of human CYP3A4 in human pooled liver microsomes in presence of testosterone as substrate preincubated for 30 mins in presence of NADPH followed by addition of substrate by LC-MS/MS analysis
- ChEMBL_2109894 (CHEMBL4818569) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate incubated for 5 mins followed by NADPH addition and measured after 5 mins by LC/MS/MS analysis
- ChEMBL_2124740 (CHEMBL4833973) Inhibition of CYP3A4 in pooled human liver microsomes using midazolam or testosterone as substrate preincubated for 30 mins in presence of NADPH followed by substrate addition by LC-MS/MS analysis
- ChEMBL_2248279 (CHEMBL5162489) Inhibition of CYP3A4 in human liver microsomes using testosterone as a substrate preincubated for 10 mins followed by NADPH addition and measured after 10 mins by LC/MS/MS analysis
- ChEMBL_2296579 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
- ChEMBL_2296589 Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate assessed as reduction in substrate hydroxylation incubated for 30 mins in presence of beta-NADPH measured by LC-MS/MS analysis
- ChEMBL_762463 (CHEMBL1816733) Inhibition of 17Beta-HSD3 expressed in intact HEK293 cells assessed as transformation of [14C]-4-androstene-3,17-dione into [14C]-testosterone in presence of NADPH after 1 hr incubation
- ChEMBL_1274566 (CHEMBL3091166) Inhibition of 17beta-HSD3 in rat testes microsomal fraction using [14C]-4-androstene-3,17-dione as substrate assessed as testosterone formation after 2 hrs by thin layer chromatography
- ChEMBL_1488503 (CHEMBL3536345) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by 10-fold dilution and substrate addition by LC-MS/MS analysis
- ChEMBL_1488505 (CHEMBL3536347) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 90 mins followed by 10-fold dilution and substrate addition by LC-MS/MS analysis
- ChEMBL_1512779 (CHEMBL3611372) Time dependent inhibition of CYP3A4 in human liver microsomes assessed as reduction in testosterone 6beta-hydroxylation incubated for 60 mins in presence of NADPH generating system by LC-MS/MS method
- ChEMBL_1797910 (CHEMBL4270027) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by substrate/NADPH addition measured after 10 mins by LC-MS/MS analysis
- ChEMBL_1870803 (CHEMBL4371970) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH cofactor addition and measured after 10 mins by LC-MS/MS analysis
- ChEMBL_2025116 (CHEMBL4678929) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH generating system addition and measured after 120 mins by LC-MS/MS
- ChEMBL_2200324 (CHEMBL5112840) Inhibition of CYP3A4 in human liver microsomes assessed as reduction in 6beta-hydroxytestosterone metabolite formation using testosterone as substrate incubated for 30 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_851741 (CHEMBL2156083) Inhibition of recombinant CYP3A4 NF-14 expressed in Escherichia coli assessed as formation of 6-beta-hydroxytestosterone using testosterone as substrate after 5 mins by HPLC based UV method
- ChEMBL_1486112 (CHEMBL3532901) Inhibition of testosterone 6beta-hydroxylase activity of human recombinant CYP3A4 in presence of human P450 oxidoreductase and b5 assessed as decrease in enzyme activity preincubated for 30 mins by LC-MS/MS analysis
- ChEMBL_1486114 (CHEMBL3532903) Inhibition of testosterone 6beta-hydroxylase activity of human recombinant CYP3A5 in presence of human P450 oxidoreductase and b5 assessed as decrease in enzyme activity preincubated for 30 mins by LC-MS/MS analysis
- ChEMBL_1660998 (CHEMBL4010610) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1904874 (CHEMBL4407232) Inhibition of 17beta-HSD3 (unknown origin) expressed in human LNCAP cells assessed as reduction in [14C]-testosterone formation from [14C]-4-androstene-3,17-dione measured after 1 hr
- ChEMBL_1904878 (CHEMBL4407236) Inhibition of 17beta-HSD3 in Sprague-Dawley rat testes microsomal fraction assessed as reduction in [14C]-testosterone formation from [14C]-4-androstene-3,17-dione measured after 2 hrs
- ChEMBL_1488507 (CHEMBL3536349) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by 10-fold dilution and substrate addition by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1488509 (CHEMBL3536719) Time dependent inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 90 mins followed by 10-fold dilution and substrate addition by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1491679 (CHEMBL3536512) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate assessed as unbound inhibitor concentration required for half maximal enzyme inactivation after 2 to 10 mins by LC-MS/MS analysis
- ChEMBL_2080684 (CHEMBL4736475) Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins in presence of NADPH generating system followed by substrate addition and measured after 10 mins by LC-MS/MS analysis
- ChEMBL_1902642 (CHEMBL4404864) Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay
- ChEMBL_1657628 (CHEMBL4007098) Inhibition of 17-beta-HSD3 (unknown origin) expressed in human LNCaP cells using [14C]-4-androstene-3,17-dione as substrate assessed as reduction of [14C]-testosterone level after 1 hr by TLC method
- ChEMBL_1660935 (CHEMBL4010547) Inhibition of CYP3A4 in human liver microsomes assessed as enzyme-mediated metabolite formation using testosterone as substrate incubated for 5 mins followed by NADPH addition measured after 30 mins by LC-MS/MS analysis
- ChEMBL_1972583 (CHEMBL4605401) Inhibition of CYP3A4/5 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by substrate addition and measured after 10 to 40 mins in absence of NADPH regeneration system by UPLC-MS analysis
- ChEMBL_1972624 (CHEMBL4605442) Inhibition of CYP3A4/5 in human liver microsomes using testosterone as substrate preincubated for 30 mins followed by substrate addition and measured after 10 to 40 mins in presence of NADPH regeneration system by UPLC-MS analysis
- CYP46A1 Enzyme Assay Briefly, in a 384-well plate format, 10 uL per well of an enzyme-substrate mixture of CYP46A1 (5 uM final concentration) and Testosterone (10 mM final concentration) were dispensed to wells containing test compound. For CYP46A1 titration, 5 uL per well of serially diluted CYP46A1 (concentrations including 10 uM, 5 uM, and 2.5 uM) and Testosterone (concentration of 10 mM) were dispensed. For Testosterone titration, 5 uL per well of serially diluted Testosterone (concentrations including 10 uM, 5 uM, and 2.5 uM) and CYP46A1 (concentration of 5 uM) were dispensed. The plates were centrifuged at 1000 rpm for 30 seconds, and then sealed and incubated at 37 C. for 30 minutes. The plate was removed from the incubator, and then 10 uL per well of NADPH-generating system were dispensed to initiate the reaction. The plates were incubated at 37 C. for 15 minutes, added with 80 uL per well of 100% methanol consisting 1 ng/ml diclofenac as internal standard, and then transferred for HPLC-MS.
- Inhibition Study on the Interconversion of Testosterone to Androstenedione (4-dione) A radioactive assay was used for the enzyme kinetics in the presence of EM1404 at different concentrations for its Ki determination. Reactions were initiated by the addition of enzyme to the reaction mixture containing substrate and test compounds. After the reaction, the steroids were extracted, separated by TLC migration, and analyzed by phosphorimaging. The Km for testosterone oxidation in the absence of EM-1404, and four apparent Km values in the presence of 1, 3, 10, and 25 nM EM-1404, were determined. Ki value was further determined by a plot of Km vs. the inhibitor concentration.
- Aromatase Assay The enzyme activity was assayed by measuring the 3H-labeled H2O formed from [1beta,2beta-3H]testosterone during aromatization. After incubation, the reaction was terminated, and the charcoal-adsorbed steroids were separated by centrifugation. Aliquots of the supernatant were assayed for the presence of 3H-labeled H2O by counting using a liquid scintillation spectrometer.
- CYP19 Assay The enzyme activity was assayed by measuring the 3H-labeled H2O formed from [1beta,2beta-3H]testosterone during aromatization. After incubation, the reaction was terminated, and the charcoal-adsorbed steroids were separated by centrifugation. Aliquots of the supernatant were assayed for the presence of 3H-labeled H2O by counting using a liquid scintillation spectrometer.
- CYP19 Assay The enzyme activity was assayed by measuring the 3H-labeled H2O formed from [1beta, 2beta-3H] testosterone or [1beta-3H] androstenedione during aromatization. After incubation, the reaction was terminated, and the charcoal-adsorbed steroids were separated by centrifugation. Aliquots of the supernatant were assayed for the presence of 3H-labeled H2O by counting using a liquid scintillation spectrometer.
- Inhibition Assay (Testosterone Hydroxylase) To gain insight into the selectivity of the synthetic compounds, nicotine, nicotine related alkaloids and nicotine metabolites for inhibition of other CYPs, we examined the major CYP present in human liver (i.e., CYP 3A4). That the CYP2A6 inhibitors showed low or no inhibitory activity against CYP3A4 suggests that the inhibitors examined selectively inhibited CYP2A6.
- In Vitro Inhibition Assay This work was performed at the MDS Pharma Services, Pharmacology Laboratories, Taiwan. The assay was an in vitro evaluation of the ability of an extract or a pure compound to inhibit the steroid 5alpha -reductase enzyme from metabolizing testosterone into dihydrotestosterone. This is an enzyme-immunoassay (EIA) for quantitative determination of testosterone in human serum or plasma. The significance of this type of inhibition is that it can lead to eradication of benign prostatic hyperplasia (BPH). Two distinct isozymes are found in mice, rats, monkeys and humans: type 1 and II. Each of these isozymes is differentially expressed in tissues and developmental stages. In human, type 1 steroid 5alpha -reductase is predominant in the sebaceous glands of most regions of skin, including scalp and liver and is responsible for approximately one third of circulating DHT. Inhibitors of steroid 5alpha -reductase may be of benefit in the treatment of androgenetic alopecia.
- Inhibition Assay Six test compound concentrations (0.1, 0.25, 1, 2.5, 10, 25 μM in DMSO; final DMSO concentration=0.275%) are incubated with human liver microsomes (0.5 mg/mL) and NADPH (1 mM) in the presence of the probe substrate testosterone (50 μM) for 5 min at 37° C. The selective CYP3A4 inhibitor, ketoconazole, is screened alongside the test compounds as a positive control.
- Inhibition Assay The potencies of the compounds as inhibitors of human hepatic cytochromes P450 of the CYP3A subfamily (particularly CYP3A4) were assessed using well-characterized selective activities: midazolam 1'-hydroxylase (Kronbach, T., et al. Mol. Pharmacol. 36, 89-96 [1989]) and testosterone 6beta -hydroxylase (Waxman, D. J., et al. Arch. Biochem. Biophys. 263, 424-436, [1988]). For midazolam hydroxylase determination the final concentrations of microsomal protein and terfenadine substrate were 0.25 mg/mL and 2.5 uM, respectively, and the LC-MS internal standard was 1alpha -hydroxytriazolam. For testosterone hydroxylase activity the final microsomal protein concentration was 0.5 mg/mL, the substrate concentration was 50 uM and the LC-MS internal standard was D7-labeled 6beta -hydroxytestosterone. After incubation at 37 C. for 5 minutes, metabolic reactions were terminated by treatment with quench solution containing the appropriate internal standard.
- CYP3A4 Inhibition Assay The CYP3A4 inhibition assay was performed using human liver microsomes and testosterone 6'-hydroxylation as a P450 isoform-specific marker. In a total volume of 150 uL, 14C-testosterone at a final concentration of 40 uM in a 100 mM phosphate buffer (pH 7.4) was incubated in a 96-well plate with 0.3 mg/mL of human liver microsomes in an Eppendorf thermomixer at 37° C. and 400 rpm. A 1.0 uL-aliquot of the 150-fold concentrated compound stock solution, prepared in DMSO, was added to yield final inhibitor concentrations of 0, 0.1, 0.5, 1.0, 5.0, 10, 25, and 50 uM. The reaction was initiated by addition of 15 uL of the NADPH-regenerating system containing the glucose-6-phosphate dehydrogenase and terminated after 7 min with a 75 uL-aliquot of methanol. After centrifugation at 465 g and 4° C. for 20 min, a 50 uL-aliquot of the supernatant was submitted to HPLC according to the method described below.
- In Vitro Testing of Androgen Receptor Assay Determination of In Vitro Pharmacological Activity. The human androgen receptor (AR) assay was run using Product #IB03001 from Indigo Biosciences. The cell line provided in this kit carries a reporter gene, induced upon AR stimulation. This reporter gene is cDNA encoding for beetle luciferase, a 62 kD protein originating from the North American firefly (Photinus pyralis). This luciferase catalyzes the mono-oxidation of D-luciferin yielding oxyluciferin, adenosine monophosphate, pyrophosphate, CO2, and photon emission. The luminescence intensity of the reaction is quantified using a luminometer. To run the assay, the cells are thawed by adding pre-warmed cell recovery medium to each tube, then placed in a 37° C. water bath. 30000 viable cells in 200 μl are plated (collagen coated plates) and incubated at 37° C., ≥85% humidity, 5% CO2 for 24 hours. Media is replaced with compound screening medium. Cells are then challenged with 125 pM (EC80) 6a-Fl Testosterone and compounds are applied in half logarithmic dilutions from 10 μM to 10 nM. Assay plates are then incubated at 37° C., ≥85% humidity, 5% CO2 for 22-24 hours. Media is replaced with luciferase detection reagent and allowed 5 minutes to equilibrate prior to luminescence quantification. Data Analysis consisted of calculating percentage of control between 100% (Negative control:6a-Fl Testosterone) and 0 (positive control: no 6a-FL Testosterone). Fitting of normalized values was made 4-Parameter sigmoidal binding curve (Log[conc]) vs. signal.
- Receptor Binding Assay Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity. The test was carried out as test above, with the following modifications: cytosol from androgen receptor-expressing insect cells (Hi5) was used, and the reference substance was 3H-testosterone.
- CYP Inhibition Assay Incubation of phenacetin, diclofenac, dextromethorphan, mephenotoin, albendazole and testosterone with human liver microsomes in the presence of in each case eight different concentrations of a compound formula (B) (as potential inhibitor) is carried out on a incubator shaker at 37 C. Standard incubation mixtures comprise NADPH and substrates in 100 mM phosphate buffer (pH 7.4) in a total volume of 200 μl. Test compound are dissolved in acetonitrile. Incubated with pooled human liver microsomes at 37° C. for a defined time. The reactions are stopped by adding 100 μl of acetonitrile in which a suitable internal standard is always present. Precipitated proteins are removed by centrifugation, and the supernatants analyzed by LC-MS/MS.
- Cyp Inhibition For Cyp inhibition, human liver microsomes from BD Gentest were incubated with Compound 028 or Compound 032 (10, 3.33, 1.11, 0.37, 0.12, 0.04, 0.01 uM) and substrate (CYP1A2: Phenacetin at 30 uM; CYP2C9: Diclofenac at 10 uM; CYP2C19: S-Mephenytoin at 35 uM; CYP3A4: Midazolam at 5 uM and Testosterone at 80 uM; CYP2D6: Bufuralol at 10 uM) for the following incubation times: CYP1A2, 2C9, 2D6: 10 minutes, 37° C.; CYP2C19: 45 minutes, 37° C.; CYP3A4: 5 minutes, 37° C. Substrate conversion was measured by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Inhibition was calculated by curve fitting in Graph Pad Prism.
- Cyp inhibition For Cyp inhibition, human liver microsomes from BD Gentest were incubated with Compound 028 or Compound 032 (10, 3.33, 1.11, 0.37, 0.12, 0.04, 0.01 μM) and substrate (CYP1A2: Phenacetin at 30 μM; CYP2C9: Diclofenac at 10 μM; CYP2C19: S-Mephenytoin at 35 μM; CYP3A4: Midazolam at 5 μM and Testosterone at 80 μM; CYP2D6: Bufuralol at 10 μM) for the following incubation times: CYP1A2, 2C9, 2D6: 10 minutes, 37° C.; CYP2C19: 45 minutes, 37° C.; CYP3A4: 5 minutes, 37° C. Substrate conversion was measured by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Inhibition was calculated by curve fitting in Graph Pad Prism.
- GTPγS Assay The [35S]GTPγS assay was incubated in 20 mM HEPES pH7.4, 100 mM NaCl, 10 μg/ml saponin, 30 mM of MgCl2, 10 μM of GDP, 5 μg membrane-expressing hGPR43, 250 μg of wheatgerm agglutinin beads (Amersham, ref: RPNQ001), a range concentration of compounds of the invention (from 30 μM to 1 nM) in a final volume of 100 μl for 30 min at room temperature. The SCFA propionate was used at 1 mM final concentration as positive control. The plates were then centrifuged for 10 minutes at 2000 rpm, incubated for 2 hours at room temperature and counted for 1 min in a scintillation counter (TopCount, PerkinElmer). The results of the tested compounds are reported as the concentration of the compound required to reach 50% (EC50) of the maximum level of the activation induced by these compounds.
- CYP450 Inhibition Assay The ability of the R and S enantiomers of (4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol to inhibit the common drug metabolizing isoforms of cytochrome P450 (CYP) was evaluated against the following isoforms: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The compounds were incubated in duplicate with eight test compound concentrations (final DMSO concentration of 0.20%) with human liver microsomes (0.25 or 0.50 mg/mL) and NADPH (1 mM) in the presence of CYP isoform specific probe substrates (phenacetin, bupropion, taxol, diclofenac, mephenyloin, dextromethorphan, testosterone) at the Km for 10-20 minutes at 37° C. Selective CYP isoform inhibitors (furafulline, ticlopidine, quercetin, sulfaphenazole, ticlopidine, quinidine, ketoconazole) were screened alongside the test compounds as positive controls.
- GTPγS Assay The assay was used to determine the activity of the compounds of the invention.The [35S]GTPγS assay was incubated in 20 mM HEPES pH7.4, 100 mM NaCl, 10 μg/ml saponin, 30 mM of MgCl2, 10 μM of GDP, 5 μg membrane-expressing hGPR43, 250 μg of wheatgerm agglutinin beads (Amersham, ref: RPNQ001), a range concentration of compounds of the invention (from 30 μM to 1 nM) in a final volume of 100 μl for 30 min at room temperature. The SCFA propionate was used at 1 mM final concentration as positive control. The plates were then centrifuged for 10 minutes at 2000 rpm, incubated for 2 hours at room temperature and counted for 1 min in a scintillation counter (TopCount, PerkinElmer). The results of the tested compounds are reported as the concentration of the compound required to reach 50% (EC50) of the maximum level of the activation induced by these compounds
- GTPγS Binding Assay The assay was used to determine the activity of the compounds of the invention. The [35S]GTPγS assay was incubated in 20 mM HEPES pH7.4, 100 mM NaCl, 10 μg/ml saponin, 30 mM of MgCl2, 10 μM of GDP, 5 μg membrane-expressing hGPR43, 250 μg of wheatgerm agglutinin beads (Amersham, ref: RPNQ001), a range concentration of compounds of the invention (from 30 μM to 1 nM) in a final volume of 100 μl for 30 min at room temperature. The SCFA propionate was used at 1 mM final concentration as positive control. The plates were then centrifuged for 10 minutes at 2000 rpm, incubated for 2 hours at room temperature and counted for 1 min in a scintillation counter (TopCount, PerkinElmer). The results of the tested compounds are reported as the concentration of the compound required to reach 50% (EC50) of the maximum level of the activation induced by these compounds.
- Inhibition Assay The CYP3A4 inhibition assays were conducted using Human Liver Microsomes purchased from Invitrogen and designed to screen potential inhibitors of Cytochrome P450 in physiological condition. Initially the following reagents/mixtures were prepared: (i) Assay buffer: 0.1 M Phosphate buffer pH 7.4 (ii) Cofactor: 15 mM stock was prepared in assay buffer. Final concentration in assay 1.5 mM (iii) Substrate 50 mM DMSO stock was prepared for testosterone. From this a 10 mM sub-stock was prepared in MeCN. Further, a working stock solution of 700 μM was prepared in assay buffer. Final concentration in assay 70 μM (iv) Enzyme: 20 mg/mL stock was provided by manufacturer. Final concentration in assay was 0.5 mg/mL. At the start of the experiment, various concentrations of compound (7 different concs.) or positive control (Ketoconazole at a single concentration) were prepared in assay buffer. For 100 μL of final reaction system, 2.5 μL of HLM (20 mg/ml), 50 μL of test compound/reference compound from each concentration was added. Subsequently, 10 μL of substrate (testosterone 700 μM) and 10 μL of Cofactor (NADPH; 15 mM) were added. The volume was increased to 100 μL by adding assay buffer. DMSO concentration was kept as 0.5% uniform across all the reactions. The reaction was then allowed to incubate for 45 min at 37° C. After completion of the incubation period, the reaction was terminated by addition of 200 μL of chilled MeCN containing internal standard (Dexamethasone). The samples were than centrifuged and supernatants were analyzed using LCMS/MS.
- CYP Activity Assay Inhibition of hepatic cytochromes P450 was assessed in human liver microsomes using a substrate-specific approach of monitoring metabolites formed by each specific CYP enzyme. Metabolic reactions included phenacetin-O-deethylation (1A2), tolbutamide methylhydroxylation (2C9), S-mephenytoin 4'-hydroxylation (2C19), dextrome-thorphan-O-deethylation (2D6), and testosterone-6-β-hydroxylation (3A4). Each substrate was added at a concentration less than or equal to the Km for themetabolic pathway, and microsomal protein concentrations and assay incubation times were optimized for each reaction to ensure linear metabolite formation based on initial rates (Table 1). Microsomes were suspended in phosphate buffer and incubated at 37 °C in the presence of probe substrates. Reactions were initiated by the addition of an NADPH-regenerating buffer system and were quenched at the appropriate times using acetonitrile. Samples were centrifuged and concentrations of metabolites assessed by LC/MS.
- Androgen Receptor (AR) Radioligand Binding Assay Human androgen receptors obtained from human LNCaP cells are used in modified HEPES buffer pH 7.4. A 70 μg (adjusted if necessary) aliquot is incubated with 0.5 nM [3H]Methyltrienolone for 20 hours at 4 C. Non-specific binding is estimated in the presence of 1 μM testosterone. Receptors are filtered and washed, the filters are then counted to determine [3H]methyltrienolone specifically bound (Historic values: Kd=0.71 nM: Specific binding=75%; Bmax=0.25 pmole/mg protein). (See, e.g., Traish, A. M et al., Binding of 7α, 17α-dimethyl-19-nortestosterone (Mibolerone) to androgen and progesterone receptors in human and animal tissues. Endocrinology. 118(4): 1327-1333, 1986).Compounds are screened at 10 μM.Where presented, IC50 values were determined by a non-linear, least squares regression analysis using MathIQ (ID Business Solutions Ltd., UK).
- Androgen Receptor Binding Assay Androgen receptor (AR) binding affinities of test compounds were studied in cytosolic lysates obtained from ventral prostates of castrated rats by competition binding assay (Schilling K. and Liao S., The Prostate, 1984; 5(6):581-588). Cytosol preparations and 1 nM [3H]mibolerone were incubated with increasing concentrations of test compounds. To determine non-specific binding, parallel incubations were carried out using excess of unlabelled testosterone. After incubation, bound and free steroids were separated by treatment with dextran-coated charcoal suspension. Bound radioactivity was determined by counting of supernatant fraction in scintillation fluid. Radioactivity was measured using a Microbeta counter. All data points were done as quadrublicates. Dissociation constant of [3H]mibolerone for rat androgen receptor was determined by saturation binding assay obtained from ventral prostates of castrated rats essentially as described (Isomaa V. et al., Endocrinology, 1982; 111(3):833-843).
- Binding Assay Androgen receptor (AR) binding affinities of test compounds were studied in cytosolic lysates obtained from ventral prostates of castrated rats by competition binding assay (Schilling K. and Liao S., The Prostate, 1984; 5(6):581-588). Cytosol preparations and 1 nM [3H]mibolerone were incubated with increasing concentrations of test compounds. To determine non-specific binding, parallel incubations were carried out using excess of unlabelled testosterone. After incubation, bound and free steroids were separated by treatment with dextran-coated charcoal suspension. Bound radioactivity was determined by counting of supernatant fraction in scintillation fluid. Radioactivity was measured using a Microbeta counter. All data points were done as quadrublicates. Dissociation constant of [3H]mibolerone for rat androgen receptor was determined by saturation binding assay obtained from ventral prostates of castrated rats essentially as described (Isomaa V. et al., Endocrinology, 1982; 111(3):833-843).
- Discontinuous Radiometric Assay Compounds may be evaluated as selective reversible inhibitors of AKR1C3 by screening them against homogeneous recombinant AKR1C1-AKR1C4 expressed in E. coli. In each case, a discontinuous radiometric assay may be used to monitor the inhibition of progesterone reduction (20-ketosteroid reduction) catalyzed by AKR1C1, the inhibition of Δ4-AD reduction (17-ketosteroid reduction) catalyzed by AKR1C3, and the inhibition of 5α-DHT reduction (3-ketosteroid reduction) catalyzed by AKR1C2 and AKR1C4 (by measuring the formation of 20α-hydroxyprogesterone, testosterone or 3α-androstanediol by radiochromatography). Secondary screens of the compounds of interest include: (a) a full-screen against all nine human recombinant AKR enzymes to ensure there are no-intended off-target effects (in this context AKR1B10 (retinal reductase; SEQ ID NO:5) has been shown to be potently inhibited by N-phenylanthranilates) (Endo et al., 2010, Biol. Pharm. Bull. 33:886-90); (b) a screen against COX-1 and COX-2 to reaffirm that compounds do not act as NSAIDs; and (c) an expanded screen against other nuclear receptors (especially other steroid hormone receptors).
- AR Antagonism Antagonism of test compounds for AR was measured by reporter gene assay in human embryonic kidney (HEK293) cells stably transfected with an expression vector encoding full-length human AR and androgen responsive luciferase reporter gene construct (hAR/HEK293 cells). To determine antagonism for hAR, the cells were treated simultaneously with increasing concentrations of the test compound and submaximal concentration of testosterone (usually 0.45 nM). The final DMSO concentration was 1%. All test compounds were studied in triplicates. The cells were incubated for 24 before measurement of luciferase activity using Luciferase Assay System (Promega Corporation).Agonism of test compounds in AR overexpressing cells was measured by reporter gene assay in HEK293 cells stably transfected with an expression vector encoding full-length human AR and androgen responsive luciferase reporter gene construct. A clone expressing high levels of androgen receptor (5 times more than AR levels in AR-HEK293 cells) was selected to study agonism in AR overexpressing cells. To determine agonism, the cells were treated with increasing concentrations of the test compound. The final DMSO concentration was 1%. The test compounds were studied in triplicates and luciferase activity was determined as described above.
- Enzyme Activity Assay Test Example 4: 100 mM PBS buffer was formulated, which was then used to formulate 2.5 mg/ml microsome solution and 5 mM NADPH solution. The 5× concentration of the compound working solution was diluted with PBS gradient (150, 50, 15, 5, 1.5, 0.15, 0.015, 0 μM). The 5× concentration of ketoconazole working solution was diluted with PBS gradient (150, 50, 15, 5, 1.5, 0.15, 0.015, 0 μM). Dextromethorphan working solution was diluted with PBS to a concentration of 50 μM.20 μl of 2.5 mg/ml microsome solution, 20 μl of 50 μM testosterone working solution, 20 μl of MgCl2 solution and 20 μl of the compound working solution (150, 50, 15, 5, 1.5, 0.15, 0.015, 0 μM, different reaction systems for each concentration) were taken respectively and mixed well. For the positive control group, the compound was replaced with the same concentration of ketoconazole. The mixture together with 5 mM NADPH solution were pre-incubated at 37° C. for 5 minutes. After 5 minutes, 20 μl of NADPH were added to each well, the reaction was started and incubated for 30 minutes. All the incubated samples were present in duplicate. After 30 minutes, 250 μl of acetonitrile containing internal standard were added to all samples, mixed well, shaken at 800 rpm for 10 minutes, and then centrifuged at 3700 rpm for 10 minutes. 80 μl of the supernatant were taken and analyzed by LC-MS/MS.
- Enzyme Activity Assay Test Example 5: 100 mM PBS buffer was formulated, which was then used to formulate 2.5 mg/ml microsome solution and 5 mM NADPH solution. The 5× concentration of the compound working solution was diluted with PBS gradient (150, 50, 15, 5, 1.5, 0.15, 0.015, 0 μM). The 5× concentration of quinidine working solution was diluted with PBS gradient (150, 50, 15, 5, 1.5, 0.15, 0.015, 0 μM). Dextromethorphan working solution was diluted with PBS to a concentration of 50 μM.20 μl of 2.5 mg/ml microsome solution, 20 μl of 50 μM testosterone working solution, 20 μl of MgCl2 solution and 20 μl of the compound working solution (150, 50, 15, 5, 1.5, 0.15, 0.015, 0 μM, different reaction systems for each concentration) were taken respectively and mixed well. For the positive control group, the compound was replaced with the same concentration of quinidine. The mixture together with 5 mM NADPH solution were pre-incubated at 37° C. for 5 minutes. After 5 minutes, 20 μl of NADPH were added to each well, the reaction was started and incubated for 30 minutes. All the incubated samples were present in duplicate. After 30 minutes, 250 μl of acetonitrile containing internal standard were added to all samples, mixed well, shaken at 800 rpm for 10 minutes, and then centrifuged at 3700 rpm for 10 minutes. 80 μl of the supernatant were taken and analyzed by LC-MS/MS.
- CYP MUX (3A4) RI Compound dilutions and assay-ready plates were prepared on a TTP Labtech mosquito HTS. Assay conduction was fully automated on a customized Screening Platform from Caliper (now PerkinElmer) containing a Mitsubishi robotic plate handler, Liconic incubators, a Caliper Zephyr liquid handling workstation equipped with temperature-controlled deck positions, a Biotek MultiFlo dispenser and an Agilent PlateLoc heat sealer. Assay plates were Corning Costar 384 well PP plates. High throughput mass spectrometric readout was performed on a RapidFire 300 system coupled to an AB Sciex API 4000 triple quadrupole device. CYP isoform 3A4 was incubated in a separate reaction of 50 μL final volume. 25 μL of HLM (human liver microsomes, BD UltraPool 150, 0.25 mg/mL final concentration) and the respective substrate, testosterone (75 μM) for 3A4, in potassium phosphate buffer (100 mM, pH=7.4) were added to 250 nL of stamped compound solution (10 mM in DMSO). The reactions were started upon addition of 25 μL of a co-factor solution containing magnesium chloride (3.3 mM), glucose-6-phosphate (3.3 mM), glucose-6-phosphate dehydrogenase (1.4 units) and NADP (1 mM) in potassium phosphate buffer (100 mM, pH=7.4) and incubated on deck at 37° C. for 10 min. 8 μL of each reaction were transferred to the same readout plated filled with 48 μL of stop solution containing internal standards (concentration in final readout plate), 6-hydroxytestosterone-D7 (0.5 μM), 4′-hydroxydiclofenac-D4 (0.2 and dextrorphan-D3 (0.01 in acetonitrile with 0.5% formic acid. After heat sealing, plates were stored at −20° C. for at least 30 min, centrifuged and subjected directly to RapidFire/MS analysis.