Target (1)
Compound (32)
Assay (7)
ChEMBL_2285147 Inhibition of recombinant human TYK2 (870 to 1187 residues) ChEBML_1690028 Inhibition of IKKalpha in human U2OS cells assessed as decrease in FCS induced p100 phosphorylation at ser866/870 residues preincubated for 1 hr followed by FCS stimulation for 4 hrs by Western blot analysis ChEMBL_1368167 (CHEMBL3299215) Inhibition of recombinant GST-fused TYK2 kinase domain (870 to 1187) (unknown origin) harboring C1187S modification using 5-FAM-KKSRGDYMTMQIG as substrate assessed as inhibition of substrate phosphorylation by peptide mobility shift assay ChEMBL_1690028 (CHEMBL4040598) Inhibition of IKKalpha in human U2OS cells assessed as decrease in FCS induced p100 phosphorylation at ser866/870 residues preincubated for 1 hr followed by FCS stimulation for 4 hrs by Western blot analysis ChEMBL_2362258 Inhibition of recombinant human N-terminal His-tagged TYK2 JH2 domain (577 to 870 residues) expressed in Sf9 cells using N-(2-(2-(2-((3-(5-acetamido-3-(3-(N,N-dimethylsulfamoyl)phenyl)-1H-pyrrolo[2,3-c]pyridin-1-yl)propyl)amino)-2-oxoethoxy)ethoxy)ethyl)-2',7'-difluoro-3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-5-carboxamide trifluoroacetate as substrate incubated for 60 mins by TR-FRET assay Esterase Activity Assay Esterase activity assay was performed based on the method of by Verpoorte et al. [Verpoorte et al., J. Biol. Chem., 242:4221-4229] as described in previous studies [Innocenti et al., Bioorg. Med. Chem., 18:2159-2164; Akıncıoğlu et al., Arch. Pharm., 347:68-76; Akıncıoğlu et al., Bioorg. Med. Chem., 21:1379-1385]. The differences in absorbances due to the hCA I and II isoenzyme activities converting 4-nitrophenylacetate (NPA) to 4-nitrophenylate ion at 348 nm were observed in 3 min duration at room temperature using a spectrophotometer (Shimadzu, UVmini-1240 UV-VIS) [Çetinkaya et al., Arch. Pharm., 347:354-359; Aksu et al., Bioorg. Med. Chem., 21:2925-2931]. The reactants were 1.4 mL 0.05 M Tris-SO4 buffer (pH 7.4), 1 mL 3 mM NPA, 0.5 mL H2O and 0.1 mL enzyme solution making a total volume of 3 mL. A cuvette containing all reactants without the enzyme solution was used as blank. For the determination of Ki values three different bromophenols concentrations with NPA as the substrate at five different concentrations were used for making of Lineweaver-Burk curves [Lineweaver et al., J. Am. Chem. Soc., 56:656-666] as previously described [Atasever et al., Food Chem., 136:864-870; Aydin et al., Int. J. Food Propert., 18:2735-2745]. CYP3A4 Inhibitory Activity Assay Test compounds, DMSO (negative control), and ketoconazole (positive control) were diluted to 4× final concentrations in water. The standard final Compound concentrations were 37, 111, 333, 1000, and 3000 nM. 12.5 μL of the Compound dilutions were transferred to a white 96-well plate. 1450 μL (enough for a whole plate) of 4× assay buffer (400 mM potassium phosphate buffer (10 mL 1M potassium phosphate buffer: 8.02 mL 1M K2HPO4 +1.98 mL 1M KH2PO4 (1.4 g K2HPO4 +0.27 g KH2PO4 in 10 mL H2O), 32 μM Luciferin-IPA (Promega V9002)) 580 μl of 1 M K3PO4 buffer, 870 μL H2O, 14 μL of 3 mM Luciferin-IPA, and 18 μL of human liver microsome (Sigma M0317-1VL) was made. 12.5 μL of 4× assay buffer was added to each well. For the well of blank control, 12.5 μL of 4× assay buffer without liver microsome was added. The plate was incubated at room temperature for 15 minutes. 2.75 mL NADPH buffer was made as follows: 2.42 mL H2O, 275 μL solution A and 55 μL solution B (NADPH regeneration system, Promega V9510). 25 μL of the buffer was added to each well. The plates were incubated at 37° C. for 11 minutes. 50 μL of luciferin detection reagent (Promega V9002) was added and the plates were incubated at room temperature for 5 minutes. The plate was read with a luminometer.
US10730877, Example 870 BDBM428434 US10544143, Example 870 US11053244, Example 870
BDBM274084 US10478424, Example 870 US10071079, Example 870
US10273259, Example 870 US10711020, Example 870 BDBM383159
US9694016, 870 US10709712, Example 870 US10245267, Example 878 BDBM87844
BDBM217610 US9212182, 870
BDBM99121 US8497265, 870
US9120749, 870 BDBM177503
US9302989, 870 BDBM216180
BDBM545381 US11286268, Compound 870
BDBM666836 US20240116946, Example 870
US10660877, Example 870 BDBM444280
US11292791, Example 870 BDBM547597
US11524959, Compound 870. BDBM583978
US20160046618, Example 870 BDBM705744
BDBM424415 US10508120, Compound I-870
BDBM566300 US11414431, Compound I-870
US12221453, Compound I-870 BDBM719922
US11046698, Compound I-763 US10508120, Compound I-763 BDBM424308 US10577373, Compound I-870 US10508120, Compound I-870
BDBM547195 US11292791, Example 870 US11292791, Example 468
BDBM623850 US11780845, Example 870 US11780845, Example 879
US8703768, 196 Roche-Dataset for PDE10A, Compound 870 BDBM120596
5-(4-(2-Methoxyphenoxy)-2-methylphenyl)-4-oxo-N-(piperidin-3- yl)-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide; US10800792, Example 870 BDBM468195 US10822348, Example 870
BDBM337585 5-[3-Fluoro-2'-(1H-pyrazol-4- yl)biphenyl-4-yl]pyrazin-2-amine US9745328, Compound 870
US12011444, Example 870 (4-{6-[2-(2-Cyano-4-methoxy-indol-1-yl)-ethylamino]-pyrimidin-4-yl}-2-ethoxy- phenoxy)-acetic acid BDBM680655
8-[4-(5-fluoro-2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1,3-diazaspiro[4.5]dec-7-ene-2,4-dione BDBM353638 US9796708, Example 870
BDBM433166 5-cyclopropyl-N-((1R,3r,5S)-8-((4-((2- methoxyethyl)amino)piperidin-1- yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3- yl)isoxazole-3-carboxamide US10577363, Compound 870
US11066414, Compound 870 BDBM506220 (S)-6-(((2-(2,2-difluoroethyl)-1-oxo-1,2- dihydroisoquinolin-5-yl)(1-(1- (difluoromethyl)cyclopropyl)-1H-1,2,3-triazol- 4-yl)methyl)amino)-4- (neopentylamino)quinoline- 3,8-dicarbonitrile
5-[4-amino-5- (trifluoromethyl)pyrrolo[2,1- f][1,2,4]triazin-7-yl]-4-fluoro-N- [(3R,4S)-4-fluoro-1-(3,3,3- trifluoro-2,2- dimethylpropanoyl)pyrrolidin-3- yl]-2-methoxybenzamide BDBM599676 US11618753, Example 870
BDBM407925 (R)-methyl 4-(5-((2-(3- cyanopyrrolo[1,2-b] pyridazin-7-yl)-5- ((2-fluoro-3-hydroxy-3- methylbutyl)carbamoyl) pyridin-4-yl)amino) pyridin-2-yl)piperazine-1- carboxylate US10336762, Compound 870
US20240148821, Compound 870 (3S,9S,18S,21S,25R,28S,31S,34S)-31-benzyl-9-[(4-chlorophenyl)methyl]-36,36-difluoro-28-isobutyl-7,10,13,16,21,22,25,29,32-nonamethyl-18-[(1S)-1-methylpropyl]-3-[2-[4-(trifluoromethyl)phenyl]ethyl]-1,4,7,10,13,16,19,22,26,29,32-undecazabicyclo[32.3.0]heptatriacontane-2,5,8,11,14,17,20,23,27,30,33-undecone BDBM671755
BDBM673684 US20240150293, Example 870 (1r,2′S,4S)-4-(3-chloroanilino)-6′-(hydroxymethyl)-2′-[(2R)-2-methyl-3-{[(5R)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2′,3′-dihydrospiro[cyclohexane-1,1′-indene]-4-carboxylic acid
BDBM673683 (1r,2′R,4R)-4-(3-chloroanilino)-6′-(hydroxymethyl)-2′-[(2R)-2-methyl-3-{[(5R)-5-methyl-5,6,7,8-tetrahydroquinolin-4-yl]oxy}propyl]-2′,3′-dihydrospiro[cyclohexane-1,1′-indene]-4-carboxylic acid US20240150293, Example 870 US20240150293, Example 869