In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans

Drug Metabolism and Disposition

Volumn 37, Issue 7, 2009, Pages 1378-1394

  Li, Chun ^a,b   Kuchimanchi, Mita ^a   Hickman, Dean ^a   Poppe, Leszek ^a   Hayashi, Mike ^a   Zhou, Yihong ^a   Subramanian, Raju ^a   Kumar, Gondi ^a,c   Surapaneni, Sekhar ^a,c  

^a AMGEN INC   (United States)

^b GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^c CELGENE CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILIRUBIN; CYTOCHROME P450 1A; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; GLUCOSAMINE DERIVATIVE; GLUCOSE; GLUCURONIDE; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A4; IMIPRAMINE; INDOLINE NITROGEN; MOTESANIB; N CARBAMOYL GLUCURONIDE; N LINKED BETA N ACETYLGLUCOSAMINE; NITROGEN DERIVATIVE; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BIOTRANSFORMATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG METABOLISM; DRUG STRUCTURE; ENZYME INHIBITION; GLUCURONIDATION; HUMAN; HUMAN CELL; LIVER CELL; MALE; MICROSOME; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; RAT; TANDEM MASS SPECTROMETRY;

ADMINISTRATION, ORAL; BIOTRANSFORMATION; CYTOCHROME P-450 ENZYME SYSTEM; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HEPATOCYTES; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INDOLES; MAGNETIC RESONANCE SPECTROSCOPY; METABOLIC NETWORKS AND PATHWAYS; METABOLOME; MICROSOMES, LIVER;

EID: 67649389517     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.108.025742     Document Type: Article

References (30)

1. Babu SR, Lakshmi VM, Hsu FF, Zenser TV, and Davis BB (1992) Role of N-glucuronidation in benzidine-induced bladder cancer in dog. Carcinogenesis 13:1235-1240.
2. Baillie TA, Cayen MN, Fouda H, Gerson RJ, Green JD, Grossman SJ, Klunk LJ, LeBlanc B, Perkins DG, and Shipley LA (2002) Drug metabolites in safety testing. Toxicol Appl Pharmacol 182:188-196.
3. Beconi MG, Mao A, Liu DQ, Kochansky C, Pereira T, Raab C, Pearson P, and Lee Chiu SH (2003) Metabolism and pharmacokinetics of a dipeptidyl peptidase IV inhibitor in rats, dogs, and monkeys with selective carbamoyl glucuronidation of the primary amine in dogs. Drug Metab Dispos 31:1269-1277. (Pubitemid 37152979)
4. Chang M, Sood VK, Kloosterman DA, Hauer MJ, Fagerness PE, Sanders PE, and Vrbanac JJ (1997) Identification of the metabolites of the HIV-1 reverse transcriptase inhibitor delavirdine in monkeys. Drug Metab Dispos 25:814-827. (Pubitemid 27318600)
5. Chiu SH and Huskey SW (1998) Species differences in N-glucuronidation. Drug Metab Dispos 26:838-847. (Pubitemid 28452049)
6. Clarke NJ, Rindgen D, Korfmacher WA, and Cox KA (2001) Systematic LC/MS metabolite identification in drug discovery. Anal Chem 73:430A-439A. (Pubitemid 32862353)
7. 3 antagonist in rats, dogs, and monkeys. Drug Metab Dispos 32:848-861.
8. Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20:4368-4380. (Pubitemid 35266299)
9. Elvin AT, Keenaghan JB, Byrnes EW, Tenthorey PA, McMaster PD, Takman BH, Lalka D, Manion CV, Baer DT, Wolshin EM, et al. (1980) Tocainide conjugation in humans: novel biotransformation pathway for a primary amine. J Pharm Sci 69:47-49. (Pubitemid 10136818)
10. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, and Zbaida S (2004) Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil). Drug Metab Dispos 32:267-271.
11. Green MD and Tephly TR (1998) Glucuronidation of amine substrates by purified and expressed UDP-glucuronosyltransferase proteins. Drug Metab Dispos 26:860-867. (Pubitemid 28452052)
12. Hastings KL, El-Hage J, Jacobs A, Leighton J, Morse D, and Osterberg RE (2003) Drug metabolites in safety testing. Toxicol Appl Pharmacol 190:91-92; author reply 93-94.
13. Heinrich MC, Blanke CD, Druker BJ, and Corless CL (2002) Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20:1692-1703. (Pubitemid 34260552)
14. Levsen K, Schiebel HM, Behnke B, Dötzer R, Dreher W, Elend M, and Thiele H (2005) Structure elucidation of phase II metabolites by tandem mass spectrometry: an overview. J Chromatogr A 1067:55-72. (Pubitemid 40363390)
15. Ma S, Chowdhury SK, and Alton KB (2006) Application of mass spectrometry for metabolite identification. Curr Drug Metab 7:503-523.
16. Marschall HU, Griffiths WJ, Zhang J, Wietholtz H, Matern H, Matern S, and Sjövall J (1994) Positions of conjugation of bile acids with glucose and N-acetylglucosamine in vitro. J Lipid Res 35:1599-1610. (Pubitemid 24291221)
17. Murphy PJ (1973) Enzymatic oxidation of nicotine to nicotine 1′(5′) iminium ion. A newly discovered intermediate in the metabolism of nicotine. J Biol Chem 248:2796-2800.
18. Nassar AE and Talaat RE (2004) Strategies for dealing with metabolite elucidation in drug discovery and development. Drug Discov Today 9:317-327. (Pubitemid 38373651)
19. Obach RS, Cox LM, and Tremaine LM (2005) Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos 33:262-270. (Pubitemid 40216594)
20. Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, and Coe JW (2006) Metabolism and disposition of varenicline, a selective α4β2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos 34:121-130. (Pubitemid 43042653)
21. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, and Tsutsui M (1996) Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica 26:681-693. (Pubitemid 26233022)
22. Polverino A, Coxon A, Starnes C, Diaz Z, DeMelfi T, Wang L, Bready J, Estrada J, Cattley R, Kaufman S, et al. (2006) AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and Kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res 66:8715-8721. (Pubitemid 44449188)
23. Rose J and Castagnoli N Jr (1983) The metabolism of tertiary amines. Med Res Rev 3:73-88. (Pubitemid 13150205)
24. Rosen LS, Kurzrock R, Mulay M, Van Vugt A, Purdom M, Ng C, Silverman J, Koutsoukos A, Sun YN, Bass MB, et al. (2007) Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors. J Clin Oncol 25:2369-2376. (Pubitemid 46999207)
25. Schaefer WH (1992) Formation of a carbamoyl glucuronide conjugate of carvedilol in vitro using dog and rat liver microsomes. Drug Metab Dispos 20:130-133.
26. Song S, Ewald AJ, Stallcup W, Werb Z, and Bergers G (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870-879. (Pubitemid 41486287)
27. Streeper RT, Pearson PG, Zhao Z, Mizsak SA, Sanders PE, Wienkers LC, and Vrbanac JJ (1997) In vitro metabolic transformations of 2,4- dipyrrolidinylpyrimidine: a chemical probe for P450-mediated oxidation of tirilazad mesylate. Xenobiotica 27:1131-1145.
28. Tang BK (1990) Drug glucosidation. Pharmacol Ther 46:53-56. (Pubitemid 20067880)
29. Toide K, Terauchi Y, Fujii T, Yamazaki H, and Kamataki T (2004) Uridine diphosphate sugar-selective conjugation of an aldose reductase inhibitor (AS-3201) by UDPglucuronosyltransferase 2B subfamily in human liver microsomes. Biochem Pharmacol 67:1269-1278. (Pubitemid 38315092)
30. Vickers S and Polsky SL (2000) The biotransformation of nitrogen containing xenobiotics to lactams. Curr Drug Metab 1:357-389.