Identification and characterization of CINPA1 metabolites facilitates structure-activity studies of the constitutive androstane receptor

Drug Metabolism and Disposition

Volumn 44, Issue 11, 2016, Pages 1759-1770

  Cherian, Milu T ^a   Yang, Lei ^a   Chai, Sergio C ^a   Lin, Wenwei ^a   Chen, Taosheng ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3 AMINO 10,11 DIHYDRO 5H DIBENZ[B,F]AZEPIN 5 YL) 2 (ETHYLAMINO)ETHAN 1 ONE; CINPA1; CONSTITUTIVE ANDROSTANE RECEPTOR; CYTOCHROME P450; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DRUG METABOLITE; ETHYL [5 (N ETHYLGLYCYL) 10,11 DIHYDRO 5H DIBENZ[B,F]AZEPIN 3 YL]CARBAMATE; HORMONE RECEPTOR BLOCKING AGENT; RECOMBINANT ENZYME; UNCLASSIFIED DRUG; BENZAZEPINE DERIVATIVE; CELL RECEPTOR; CYTOCHROME P450 2B6; CYTOCHROME P450 3A; ETHYL (5-(DIETHYLGLYCYL)-10,11-DIHYDRO-5H-DIBENZO(B,F)AZEPIN-3-YL)CARBAMATE; LIGAND;

ANIMAL CELL; ARTICLE; BIOCHEMICAL ANALYSIS; CONTROLLED STUDY; DRUG BINDING SITE; DRUG EFFECT; DRUG IDENTIFICATION; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; ENZYME ASSAY; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; LIGAND BINDING; LIVER MICROSOME; MALE; MOLECULAR DOCKING; MOLECULAR INTERACTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REPORTER GENE; SECONDARY METABOLISM; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; ANIMAL; CACO-2 CELL LINE; DRUG EFFECTS; HEP-G2 CELL LINE; LIVER CELL; METABOLISM; PHYSIOLOGY; TUMOR CELL LINE;

ANIMALS; BENZAZEPINES; CACO-2 CELLS; CELL LINE, TUMOR; CYTOCHROME P-450 CYP2B6; CYTOCHROME P-450 CYP3A; GENES, REPORTER; HEP G2 CELLS; HEPATOCYTES; HUMANS; LIGANDS; MICE; MICROSOMES, LIVER; RECEPTORS, CYTOPLASMIC AND NUCLEAR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84990858758     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.116.071993     Document Type: Article

References (33)

1. Achour B, Barber J, and Rostami-Hodjegan A (2014) Expression of hepatic drug-metabolizing cytochrome p450 enzymes and their intercorrelations: a meta-analysis. Drug Metab Dispos 42: 1349-1356.
2. Bertilsson L, Dahl ML, Dalén P, and Al-Shurbaji A (2002) Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 53:111-122.
3. Cherian MT, Chai SC, and Chen T (2015a) Small-molecule modulators of the constitutive androstane receptor. Expert Opin Drug Metab Toxicol 11:1099-1114.
4. Cherian MT, Lin W, Wu J, and Chen T (2015b) CINPA1 is an inhibitor of constitutive androstane receptor that does not activate pregnane X receptor. Mol Pharmacol 87:878-889.
5. Desta Z, Kerbusch T, Soukhova N, Richard E, Ko JW, and Flockhart DA (1998) Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. J Pharmacol Exp Ther 285:428-437.
6. Evans WE and Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286:487-491.
7. Fabre G, Julian B, Saint-Aubert B, Joyeux H, and Berger Y (1993) Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab Dispos 21: 978-985.
8. Fukami T and Yokoi T (2012) The emerging role of human esterases. Drug Metab Pharmacokinet 27:466-477.
9. Goodwin B, Hodgson E, D'Costa DJ, Robertson GR, and Liddle C (2002) Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor. Mol Pharmacol 62: 359-365.
10. Guengerich FP, Gillam EMJ, Martin MV, Baba T, Kim BR, Shimada T, Raney KD, and Yun CH (1994) The importance of cytochrome P450 3A enzymes in drug metabolism, in Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research (Waterman MR and Hildebrand M eds) pp 161-186, Springer-Verlag, Berlin.
11. Hodgson E (2001) In vitro human phase I metabolism of xenobiotics I: pesticides and related chemicals used in agriculture and public health, September 2001. J Biochem Mol Toxicol 15: 296-299.
12. Honkakoski P, Sueyoshi T, and NegishiM (2003) Drug-activated nuclear receptors CAR and PXR. Ann Med 35:172-182.
13. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, Ikeda T, and Kurihara A (2010) Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 38:92-99.
14. Laskowski RA and Swindells MB (2011) LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778-2786.
15. Li L, Sinz MW, Zimmermann K, and Wang H (2012) An insulin-like growth factor 1 receptor inhibitor induces CYP3A4 expression through a pregnane X receptor-independent, noncanonical constitutive androstane receptor-related mechanism. J Pharmacol Exp Ther 340:688-697.
16. Lin W, Yang L, Chai SC, Lu Y, and Chen T (2016) Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor. Eur J Med Chem 108:505-528.
17. Meunier B, de Visser SP, and Shaik S (2004) Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes. Chem Rev 104:3947-3980.
18. Oda S, Fukami T, Yokoi T, and Nakajima M (2015) A comprehensive review of UDPglucuronosyltransferase and esterases for drug development. Drug Metab Pharmacokinet 30: 30-51.
19. Ortiz de Montellano P and De Voss J (2005) Substrate oxidation by cytochrome P450 enzymes, in Cytochrome P450 (Ortiz de Montellano P ed) pp 183-245, Springer, New York.
20. Paar WD, Poche S, Gerloff J, and Dengler HJ (1997) Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. Eur J Clin Pharmacol 53:235-239.
21. Rae JM, Soukhova NV, Flockhart DA, and Desta Z (2002) Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolism. Drug Metab Dispos 30:525-530.
22. Rakesh BD, Bruhn D, Madhura DB, Maddox M, Lee RB, Trivedi A, Yang L, Scherman MS, Gilliland JC, Gruppo V, et al. (2012) Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties. Bioorg Med Chem 20:6063-6072.
23. Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, et al. (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302:1429-1436.
24. Sueyoshi T, Kawamoto T, Zelko I, Honkakoski P, and Negishi M (1999) The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J Biol Chem 274:6043-6046.
25. Timsit YE and Negishi M (2007) CAR and PXR: the xenobiotic-sensing receptors. Steroids 72: 231-246.
26. Trott O and Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455-461.
27. Uchida M, Fukazawa T, Yamazaki Y, Hashimoto H, and Miyamoto Y (2009) A modified fast (4 day) 96-well plate Caco-2 permeability assay. J Pharmacol Toxicol Methods 59:39-43.
28. Walsky RL and Obach RS (2004) Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647-660.
29. Wang H, Faucette S, Sueyoshi T, Moore R, Ferguson S, Negishi M, and LeCluyse EL (2003) A novel distal enhancer module regulated by pregnane X receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression. J Biol Chem 278:14146-14152.
30. Wang JS, Backman JT, Taavitsainen P, Neuvonen PJ, and Kivistö KT (2000) Involvement of CYP1A2 and CYP3A4 in lidocaine N-deethylation and 3-hydroxylation in humans. Drug Metab Dispos 28:959-965.
31. Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, and Desta Z (2003) The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 306:287-300.
32. Willson TM and Kliewer SA (2002) PXR, CAR and drug metabolism. Nat Rev Drug Discov 1: 259-266.
33. Zanger UM and Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138:103-141.