2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one BUPROPION BUPROPION HYDROCHLORIDE BDBM50048392 CHEMBL894 US9944618, Compound ID No. 176
BW-323 Bupropion Wellbutrin CHEMBL1698 Wellbutrin xl BUPROPION HYDROCHLORIDE 2-tert-Butylamino-1-(3-chloro-phenyl)-propan-1-one; hydrochloride Zyban Amfebutamone Hydrochloride Wellbutrin sr BDBM50290504
- Shi, Y; Dinh, J; Pelletier, R; Raccor, B; Yusuff, N; Morgan, AJ; Harbeson, S; Uttamsingh, V; Totah, RA Selective deuteration of bupropion slows epimerization and reduces metabolism. Bioorg Med Chem Lett 76: (2022)
- Carroll, FI; Blough, BE; Abraham, P; Mills, AC; Holleman, JA; Wolckenhauer, SA; Decker, AM; Landavazo, A; McElroy, KT; Navarro, HA; Gatch, MB; Forster, MJ Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. J Med Chem 52: 6768-81 (2009)
- Carroll, FI; Blough, BE; Mascarella, SW; Navarro, HA; Eaton, JB; Lukas, RJ; Damaj, MI Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. J Med Chem 53: 2204-14 (2010)
- Lapinsky, DJ; Aggarwal, S; Nolan, TL; Surratt, CK; Lever, JR; Acharya, R; Vaughan, RA; Pandhare, A; Blanton, MP (±)-2-(N-tert-Butylamino)-3'-[(125)I]-iodo-4'-azidopropiophenone: a dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban). Bioorg Med Chem Lett 22: 523-6 (2011)
- ChEMBL_2291486 Inhibition of CYP2B6 in pooled human liver microsomes using bupropion as substrate assessed as reduction in OH-bupropion metabolite formation by LC-MS/MS analysis
- ChEMBL_1435701 (CHEMBL3388334) Inhibition of CYP2B6 (unknown origin) using bupropion substrate
- ChEMBL_1487656 (CHEMBL3532642) Reversible inhibition of human CYP2B6 bupropion hydroxylase activity
- ChEMBL_1667012 (CHEMBL4016808) Inhibition of human liver microsomes CYP2B6 using bupropion as substrate
- ChEMBL_2100788 (CHEMBL4809184) Direct inhibition of CYP2B6 in human liver microsomes using bupropion as substrate
- ChEMBL_2265890 Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate by LC-MS analysis
- ChEMBL_2252747 (CHEMBL5166957) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate in presence or absence of NADPH
- ChEMBL_690369 (CHEMBL1634986) Inhibition of CYP2B6 in human liver microsomes using bupropion as probe after 10 mins
- ChEMBL_854492 (CHEMBL2160814) Inhibition of human CYP2B6 in liver microsomes assessed as bupropion hydroxylation after 48 hrs
- ChEMBL_2110154 (CHEMBL4818829) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate by LC-MS/MS analysis
- ChEMBL_2156136 (CHEMBL5040796) Inhibition of CYP2B6 in human liver microsomes using Bupropion as substrate by LC-MS/MS analysis
- ChEMBL_690366 (CHEMBL1634983) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion 4-hydroxylation after 10 mins
- ChEMBL_1526169 (CHEMBL3636694) Reversible inhibition of CYP2B6 bupropion hydroxylase activity in human liver microsomes by LC-MS/MS analysis
- ChEMBL_2100798 (CHEMBL4809194) Time-dependent inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 30 mins
- ChEMBL_2296116 Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_738480 (CHEMBL1743381) Mechanism based inhibition of human cytochrome P450 2B6 measured by bupropion hydroxylation using recombinant CYP2B6
- ChEMBL_738482 (CHEMBL1743383) Mechanism based inhibition of human cytochrome P450 2B6 measured by bupropion hydroxylation using a recombinant system
- ChEMBL_738479 (CHEMBL1743380) Mechanism based inhibition of human cytochrome P450 2B6 measured by bupropion hydroxylation using human liver microsomes
- ChEMBL_738481 (CHEMBL1743382) Mechanism based inhibition of human cytochrome P450 2B6 measured by bupropion hydroxylation using human liver microsomes
- ChEMBL_977235 (CHEMBL2416906) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion hydroxylation after 20 mins by LC-MS analysis
- ChEMBL_1281749 (CHEMBL3100518) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion hydroxylation after 20 mins by LC-MS/MS analysis
- ChEMBL_2066469 (CHEMBL4721722) Inhibition of human liver microsome CYP2B6 using bupropion as substrate incubated for 20 mins by LC-MS/MS analysis
- ChEMBL_2101772 (CHEMBL4810168) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate substrate in presence of NADPH by LC-MS/MS analysis
- ChEMBL_690376 (CHEMBL1634993) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion 4-hydroxylation after 15 mins by Dixon plot analysis
- ChEMBL_813099 (CHEMBL2020718) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins by LC-MS/MS analysis
- ChEMBL_1486257 (CHEMBL3534695) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate after 5 to 30 mins by LC-MS/MS analysis
- ChEMBL_1904191 (CHEMBL4406413) Inhibition of CYP2B6 in human pooled liver microsomes using bupropion as substrate after 10 mins by UPLC-MS/MS analysis
- ChEBML_1661006 Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 10 mins followed by NADPH addition measured after 20 mins
- ChEMBL_1492463 (CHEMBL3528838) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion hydroxylation after 3 mins by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1492473 (CHEMBL3528848) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion hydroxylation preincubated for 15 mins by LC-MS/MS analysis in presence of NADPH
- ChEMBL_1742655 (CHEMBL4158405) Inhibition of of CYP2B6 in human liver microsomes using bupropion as substrate after 10 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1904557 (CHEMBL4406779) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate incubated for 40 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1992477 (CHEMBL4626212) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate incubated for 20 mins in presence of NADPH by LC/MS/MS analysis
- ChEMBL_2253490 (CHEMBL5167700) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate incubated for 5 to 45 mins in presence of NADPH by LC/MS analysis
- ChEMBL_1481819 (CHEMBL3539940) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 20 mins with substrate prior to initiation of reaction with NADPH by HPLC analysis
- ChEMBL_1658364 (CHEMBL4007976) Inhibition of microsomal CYP2B6 (unknown origin) using bupropion as substrate preincubated for 5 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_1661006 (CHEMBL4010618) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 10 mins followed by NADPH addition measured after 20 mins
- ChEMBL_2025182 (CHEMBL4678995) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 3 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_2101710 (CHEMBL4810106) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH addition by LC-MS/MS analysis
- ChEMBL_2124310 (CHEMBL4833543) Inhibition of CYP2B6 in human liver microsomes assessed as bupropion hydroxylation reaction incubated for 30 mins in presence of NADP by LC-MS/MS analysis
- ChEMBL_1661000 (CHEMBL4010612) Inhibition of human CYP2B6 using bupropion as substrate incubated for 5 mins followed by NADPH addition measured after 30 mins by LC-MS/MS analysis
- ChEMBL_1677529 (CHEMBL4027672) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate upto 10 uM after 10 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_2293133 Activation of CYP2B6 in human hepatocyte using bupropion as substrate preincubated for 5 days followed by substrate addition and measured after 1 hr by LC-MS/MS analysis
- ChEMBL_1493635 (CHEMBL3529851) Metabolism-dependent inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 20 mins with NADPH prior to initiation of reaction with probe substrate by HPLC analysis
- ChEMBL_1764604 (CHEMBL4199851) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate pretreated for 5 mins followed by NADPH addition and measured after 10 mins by LC-MS analysis
- ChEMBL_1845025 (CHEMBL4345452) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
- ChEMBL_1902235 (CHEMBL4404457) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH addition and measured for 10 to 30 mins by LC-MS/MS analysis
- ChEMBL_2212606 (CHEMBL5125555) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH addition measured after 20 mins by LC-MS/MS analysis
- ChEMBL_2296573 Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
- ChEMBL_2296583 Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate assessed as reduction in substrate hydroxylation incubated for 30 mins in presence of beta-NADPH measured by LC-MS/MS analysis
- ChEMBL_1735366 (CHEMBL4150902) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis
- ChEMBL_1660956 (CHEMBL4010568) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins in presence of NADPH by LC-MS/MS analysis
- ChEMBL_1805640 (CHEMBL4304999) Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH-generating system addition and measured after 20 mins by LC-MS/MS analysis
- ChEMBL_1904194 (CHEMBL4406416) Inhibition of CYP2B6 in human pooled liver microsomes using bupropion as substrate preincubated with NADPH for 30 mins followed by substrate addition and measured after 10 mins by UPLC-MS/MS analysis
- ChEMBL_2080678 (CHEMBL4736469) Inhibition of CYP2B6 in human liver microsomes using bupropion 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_1660893 (CHEMBL4010505) Inhibition of CYP2B6 in human liver microsomes assessed as enzyme-mediated metabolite formation using bupropion as substrate incubated for 5 mins followed by NADPH addition measured after 30 mins by LC-MS/MS analysis
- Inhibition Assay Six test compound concentrations (0.1, 0.25, 1, 2.5, 10, 25 μM in DMSO; final DMSO concentration=0.3%) are incubated with human liver microsomes (0.1 mg/mL) and NADPH (1 mM) in the presence of the probe substrate bupropion (110 μM) for 5 min at 37° C. The selective CYP2B6 inhibitor, ticlopidine, is screened alongside the test compounds as a positive control.
- 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.
- CYP Enzyme Inhibitory Activity IC50 Assay The CYP enzyme probe substrates used in the experiment were: Phenacetin (1A2), Bupropion (2B6), Amodiaquine (2C8), Mephenytoin (2C19), Diclofenac (2C9), Dextromethorphan (2D6) and Testosterone (3A4/5). The final concentration of microsomes in the experimental system was 0.1 mg/mL. PBS Buffer was 50 mM K2HPO4 buffer. The concentrations of the compound to be tested were 50 μM, 12.5 μM, 3.125 μM, 0.781 μM, 0.195 μM, and 0.0488 μM, respectively. The corresponding probe substrates and microsomes were added into PBS, mixed well and dispensed into each reaction system, then control compound/compound to be tested/DMSO solution was added into the corresponding reaction systems respectively. The reaction system was mixed well, pre-incubated in a water bath at 37° C. for 5 minutes, added with 10 mM NADPH solution and mixed well, and reacted in a water bath at 37° C. for 10 minutes. After the reaction was completed, an internal standard acetonitrile solution was added to terminate the reaction. Centrifugation was performed at 4000 rpm, and the supernatant solution was taken and mixed well with an equal volume of pure water.
- CYP inhibitio CYP inhibition by test compounds in human liver microsomes (HLM) for seven major CYP450 isoforms CYP1A2, CYP2C9, CYP2D6, CYP2B6, CYP2C8, CYP2C19 and CYP3A4 were assessed. Reactions were performed by incubating a test compound at concentrations of 0.02, 0.070, 0.21, 0.62, 1.85, 5.56, 16.67 and 50 μM in <1% DMSO with HLM (0.2 mg/mL for CYP1A2 and 0.03 mg/ml for CYP3A4, 0.2 mg/mL for CYP2C19, CYP2D6, and CYP2C9) in 0.1M phosphate buffer, 1 mM NADPH and selective probe substrates of individual isoforms at 37° C. 50 μM phenacetin, 2 μM midazolam, 5 μM diclofenac, 50 μM mephenytoin, 80 μM bupropion, and 5 μM dextromethorphan were used as probe substrates of CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2B6, and CYP2D6, respectively. The incubation times were 20 min for CYP 1A1, CYP2D6, CYP2C9, CYP2B6, and CYP2C8; 40 min for CYP2C19; and 10 min for CYP 3A4. Following incubations, the reactions were terminated with acetonitrile containing internal standard. The samples were centrifuged and the supernatants were analyzed for the formation of metabolites (1-hydroxymidazolam (CYP3A4), 4-hydroxydiclofenac (CYP2C9), 4-hydroxymephenytoin (CYP2C19) and dextrorphan (CYP2D6), hydroxybupropion (CYP2B6), acetaminophen (CYP1A2), desethylamodiaquine (CYP2C8)) by LC/MS/MS. Selective inhibitors for all isoforms were screened alongside as positive controls. A decrease in the formation of metabolites compared to vehicle control (100%) was used to estimate % inhibition, and the IC50 was estimated from concentration-response curves.