4-[(7-chloroquinolin-4-yl)amino]-2-[(diethylamino)methyl]phenol AMODIAQUINE BDBM50041457 med.21724, Compound 188 CHEMBL682
CHEMBL1235 N-Monodesethylamodiaquine (Deaq) desethylamodiaquine 4-(7-Chloro-quinolin-4-ylamino)-2-ethylaminomethyl-phenol BDBM50056190 Monodesethylamodiaquine bidesethylamodiaquine Desethyl amodiaquine
- Lee, SG; Alpert, TD; Jez, JM Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine. Bioorg Med Chem Lett 22: 4990-3 (2012)
- O'Neill, PM; Shone, AE; Stanford, D; Nixon, G; Asadollahy, E; Park, BK; Maggs, JL; Roberts, P; Stocks, PA; Biagini, G; Bray, PG; Davies, J; Berry, N; Hall, C; Rimmer, K; Winstanley, PA; Hindley, S; Bambal, RB; Davis, CB; Bates, M; Gresham, SL; Brigandi, RA; Gomez-de-Las-Heras, FM; Gargallo, DV; Parapini, S; Vivas, L; Lander, H; Taramelli, D; Ward, SA Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. Identification of a suitable"back-up" compound for N-tert-butyl isoquine. J Med Chem 52: 1828-44 (2009)
- ChEMBL_692839 (CHEMBL1637353) Inhibition of human CYP2C8 using amodiaquine as a substrate
- ChEBML_1683158 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate
- ChEMBL_1435702 (CHEMBL3388335) Inhibition of CYP2C8 (unknown origin) using amodiaquine substrate
- ChEMBL_1667013 (CHEMBL4016809) Inhibition of human liver microsomes CYP2C8 using amodiaquine as substrate
- ChEMBL_1981694 (CHEMBL4614956) Inhibition of CYP2C8 (unknown origin) assessed as reduction in amodiaquine N-deethylation
- ChEMBL_2100789 (CHEMBL4809185) Direct inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate
- ChEMBL_2265891 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS analysis
- ChEMBL_2252748 (CHEMBL5166958) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate in presence or absence of NADPH
- ChEMBL_2282759 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_2290734 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_1824050 (CHEMBL4323814) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_1825000 (CHEMBL4324764) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_1832034 (CHEMBL4332042) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_1979600 (CHEMBL4612735) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_2022413 (CHEMBL4676226) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_2110155 (CHEMBL4818830) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_2165290 (CHEMBL5050151) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_2200574 (CHEMBL5113090) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
- ChEMBL_2100799 (CHEMBL4809195) Time-dependent inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated for 30 mins
- ChEMBL_2296117 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate in presence of NADPH by LC-MS/MS analysis
- ChEBML_1695898 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate after 10 mins by LC-MS/MS analysis
- ChEMBL_1526170 (CHEMBL3636695) Reversible inhibition of CYP2C8 amodiaquine-N-deethylase activity in human liver microsomes by LC-MS/MS analysis
- ChEMBL_2278018 Inhibition of CYP2C8 in human liver microsome suspension using amodiaquine substrate incubated for 30 mins by LC/MS analysis
- ChEMBL_1486160 (CHEMBL3533279) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate after 5 mins by LC-MS/MS analysis
- ChEMBL_2030249 (CHEMBL4684407) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate incubated for 30 mins by LC-MS/MS analysis
- ChEMBL_2035469 (CHEMBL4689627) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate incubated for 15 mins by LC-MS/MS analysis
- ChEMBL_2101773 (CHEMBL4810169) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1904192 (CHEMBL4406414) Inhibition of CYP2C8 in human pooled liver microsomes using amodiaquine as substrate after 10 mins by UPLC-MS/MS analysis
- ChEMBL_2073304 (CHEMBL4728838) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate measured after 15 mins by LC-MS/MS analysis
- ChEMBL_1742656 (CHEMBL4158406) Inhibition of of CYP2C8 in human liver microsomes using amodiaquine as substrate after 10 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1920112 (CHEMBL4422957) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate after 15 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_2209733 (CHEMBL5122682) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_1586832 (CHEMBL3826664) Inhibition of CYP2C8 in human liver microsomes in presence of NADPH using amodiaquine as substrate measured within 2.5 mins by LC-MS/MS analysis
- ChEMBL_1658365 (CHEMBL4007977) Inhibition of microsomal CYP2C8 (unknown origin) using amodiaquine as substrate preincubated for 5 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_2277113 Inhibition of CYP2C8 (unknown origin) using amodiaquine as substrate incubated for 10 to 20 mins in presence of NADPH-generating system by LC-MS/MS analysis
- ChEMBL_2291487 Inhibition of CYP2C8 in pooled human liver microsomes using amodiaquine as substrate assessed as reduction in N-desethylamodiaquine metabolite formation by LC-MS/MS analysis
- ChEMBL_2017917 (CHEMBL4671495) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate incubated for 15 mins in presence of NADPH generating system by LC-MS/MS analysis
- ChEMBL_2194838 (CHEMBL5107198) Inhibition of CYP2C8 in human liver microsomes at 10 uM using amodiaquine as substrate preincubated for 10 mins followed by NADPH addition by LC/MS analysis
- ChEBML_1688704 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated for 15 mins measured after 8 mins in presence or absence of NADPH by LC/MS/MS analysis
- ChEMBL_823394 (CHEMBL2046053) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate incubated for 3 mins prior to NAPDH-addition measured after 30 mins by RP-HPLC analysis
- ChEMBL_1845026 (CHEMBL4345453) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
- ChEMBL_1902236 (CHEMBL4404458) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
- ChEMBL_2248277 (CHEMBL5162487) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as a substrate preincubated for 10 mins followed by NADPH addition and measured after 10 mins by LC/MS/MS analysis
- ChEMBL_1735367 (CHEMBL4150903) Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis
- ChEMBL_1904187 (CHEMBL4406409) Inhibition of CYP2C8 in human pooled liver microsomes using amodiaquine as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by UPLC-MS/MS analysis
- Cytochrome P450 2C9 Inhibition Assay (Amodiaquine) The inhibition of cytochrome P450 2C8-isoenzyme catalysed deethylation of Amodiaquine by the test compound is assayed at 37° C. with human liver microsomes. All assays are carried out on a robotic system in 96 well plates. The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), human liver microsomes (0.05 mg/ml), Amodiaquine (1 uM) and the test compound at five different concentrations or no compound (high control) in duplicate (e.g. highest concentration 10-50 uM with subsequent serial 1:4 dilutions). Following a short preincubation period, reactions are started with the cofactor (NADPH, 1 mM) and stopped by cooling the incubation down to 8° C. and subsequently by addition of one volume of acetonitrile.
- ChEMBL_2080679 (CHEMBL4736470) Inhibition of CYP2C8 in human liver microsomes using amodiaquine 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
- Inhibition Assays The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
- Inhibition of CYP-2C8 The inhibition of cytochrome P450 2C8-isoenzyme catalyzed deethylation of amodiaquine by the test compound is assayed at 37° C. with human liver microsomes. All assays are carried out on a robotic system in 96 well plates. The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), human liver microsomes (0.05 mg/mL), amodiaquine (1 μM) and the test compound at five different concentrations or no compound (high control) in duplicate (e.g. highest concentration 10-50 μM with subsequent serial 1:4 dilutions). Following a short preincubation period, reactions are started with the cofactor (NADPH, 1 mM) and stopped by cooling the incubation down to 8° C. and subsequently by addition of one volume of acetonitrile. An internal standard solution the stable isotope d5-desethylamodiaquine is added after quenching of incubations. Peak area analyte (=metabolite formed) and internal standard is determined by LC-MS/MS. The resulting peak area ratio analyte to internal standard in these incubations is compared to a control activity containing no test compound. Within each of the assay runs, the IC50 of a positive control inhibitor (Montelukast) is determined. Experimental IC50 values are calculated by least square regression according to the following equation: % control activity=(100% control activity/(1+(I/IC 50)S))−B with I=inhibitor concentration; S=slope factor; B=background activity (lower plateau of the inhibition curve).
- CYP Enzyme Inhibition Assay Human liver microsomes (HLMs) (0.3 mg/mL in 0.1-M potassium phosphate buffer, pH 7.4) are incubated with CYP (cytochromes P450) isozyme-selective substrates (phenacetin for CYP1A2, amodiaquine for CYP2C8, diclofenac for CYP2C9, S-mephenytoin for CYP2C19, Dextromethorphan for CYP2D6, and midalozam for CYP3A4/5), and multiple concentrations of Compound (I-1) or Ko143 (0, 0.041, 0.12, 0.37, 1.11, 3.33, 10, and 30 uM) in 96-well plates. Reactions are initiated by the addition of β-NADPH (2 mM) and MgCl2 (3 mM) in 0.1-M potassium phosphate buffer, pH 7.4. Reactions are incubated for 12 minutes at 37° C., and then terminated by the addition of an equal volume of ACN containing 1-uM carbutamide (IS). The plates are refrigerated at approximately 4° C. for 15 minutes and then centrifuged in order to pellet the precipitated proteins.