In vitro and in vivo metabolism of the anti-cancer agent CI-1040, a MEK inhibitor, in rat, monkey, and human

Pharmaceutical Research

Volumn 21, Issue 9, 2004, Pages 1670-1679

  Wabnitz, Paul A ^a   Mitchell, David ^a   Wabnitz, David A M ^b  

^a PFIZER INC   (United States)

^b QUEEN ELIZABETH HOSPITAL   (Australia)

Author keywords

Cross species comparison; Human bile; LC MS; LC MSMS; Mass spectrometry; MEK; Metabolism; Oncology

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 2 (2 CHLORO 4 IODOPHENYLAMINO) 3,4 DIFLUOROBENZAMIDE; 2 (2 CHLORO 4 IODOPHENYLAMINO) 3,4 DIFLUOROBENZOIC ACID; ANTINEOPLASTIC AGENT; DEFLUOROHYDROXY 2 (2 CHLORO 4 IODOPHENYLAMINO) 3,4 DIFLUOROBENZAMIDE; DRUG METABOLITE; GLUCURONIDE; HYDROXY 2 (2 CHLORO 4 IODOPHENYLAMINO) 3,4 DIFLUOROBENZAMIDE; HYDROXY 2 (2 CHLORO 4 IODOPHENYLAMINO) 3,4 DIFLUOROBENZOIC ACID; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; UNCLASSIFIED DRUG; 2-(2-CHLORO-4-IODOPHENYLAMINO)-N-CYCLOPROPYLMETHOXY-3,4-DIFLUOROBENZAMIDE; BENZAMIDE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE KINASE;

ADVANCED CANCER; AEROBIC METABOLISM; AGED; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BILE; BILE DUCT; BLOOD SAMPLING; COLON CANCER; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG BILE LEVEL; DRUG BLOOD LEVEL; DRUG EXCRETION; DRUG HYDROXYLATION; DRUG IDENTIFICATION; DRUG METABOLISM; DRUG MONITORING; DRUG TOLERABILITY; DRUG URINE LEVEL; EXPERIMENTAL ANIMAL; EXPERIMENTAL MODEL; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; MONKEY; NONHUMAN; PRIORITY JOURNAL; PROCESS DEVELOPMENT; RADIOCHROMATOGRAPHY; RAT; RAT STRAIN; T TUBE; ANIMAL; BIOTRANSFORMATION; BLOOD; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; LIVER CELL; LIVER MICROSOME; MACACA; METABOLISM; WISTAR RAT;

AGED; ANIMALS; ANTINEOPLASTIC AGENTS; BENZAMIDES; BILE; BIOTRANSFORMATION; HEPATOCYTES; HUMANS; MACACA FASCICULARIS; MALE; MICROSOMES, LIVER; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MODELS, CHEMICAL; MOLECULAR STRUCTURE; RATS; RATS, WISTAR;

EID: 16844379314     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/B:PHAM.0000041464.27579.d0     Document Type: Article

References (30)

1. M. Melameds. Lung cancer screening results in the National Cancer Institute New York Study. Cancer Res. 89:2356-2362 (2000).
2. G. Brundtlan. Global Health Situation and Trends 1955-2025. Fifty Facts from The World Health Report, Wiley-Interscience, New York (1998).
3. J. Sebolt-Leopold, D. Dudley, R. Herrera, K. Van Becelaere, A. Wiland, R. Gowan, H. Tecle, S. Barrett, A. Bridges, S. Przybranowsk, W. Leopold, and L. A. Saltie. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med. 5:810-816 (1999).
4. J. Sebolt-Leopold. Development of anticancer drugs targeting the MAP kinase pathway. Oncog. 19:6594-6599 (2000).
5. L. A. Saltie. PD098059 Is a Specific Inhibitor of Mitogen-Activated Protein Kinase in vitro and in vivo. Scientist 11:12 (1997).
6. L. Pang, T. Sawada, S. J. Decker, and A. R. Saltiel. Inhibition of MAP kinase kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. J. Biol. Chem. 270:13585-13588 (1995).
7. M. Cobb and E. Goldsmith. How MAP kinases are regulated. J. Biol Chem. 270:14843-14846 (1995).
8. T. Shih, M. Weeks, P. Gruss, R. Dhar, S. Oroszlan, and E. Scolnick. Identification of a precursor in the biosynthesis of the p21 transforming protein of harvey murine sarcoma Virus. J. Virol. 42:253-261 (1982).
9. M. Streit, R. Schmidt, R. U. Hilgenfeld, E. Thiel, and E. D. Kreuser. Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. J. Mol. Med. 74:253-268 (1996).
10. S. Talapatra and C. Thompson. Growth factor signaling in cell survival: implications for cancer treatment. J. Pharm. Exp. Ther 298:873-878 (2001).
11. C. Zheng and K. Guan, Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases. J. Biol. Chem. 268:23933-23939 (1993).
12. Y. Yarden and M. Sliwkowski. Untangling the ErbB signaling network. Nat. Med. 2:127-137 (2001).
13. P. Warne and P. Viciana. and J. Downward. Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro. Nat. Med. 364:352-355 (1993).
14. S. Tanimura, Y. Chatani, R. Hoshino, M. Sato, S. Watanabe, T. Kataoka, T. Nakamura, and M. Kohno. Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering. Oncog. 17:57-65 (1998).
15. C. Simon, J. Juarez, G. Nicolson, and D. Boyd. Effect of PD 098059, a specific inhibitor of mitogen-activated protein kinase. on urokinase expression and in vitro invasion. Cancer Res. 56:5369-5374 (1996).
16. A. Shiamura, B. Ballif, and S. Richards. and J. Blenis. Rsk1 mediates a MEK-MAP kinase cell survival signal. Curr. Biol. 10:127-135 (2000).
17. G. Pages, J. Milanini, D. E. Richard, E. Berra, E. Gothie, and F. Vinals. and J. Pouyssegur. Signaling angiogenesis via p42/p44 MAP kinase cascade. Ann. N. Y. Acad. Sci. 902:187-200 (2000).
18. P. Kurada and K. White. Ras promotes cell survival in Drosophiila by down-regulating hid expression. Cell 95:319-329 (1998).
19. J. Gibbs. Mechanism-based target identification and drug discovery in cancer research. Science 287:1969-1973 (2000).
20. D. Robbins, E. Zhen, M. Cheng, S. Xu, D. Ebert, and M. Cobb. MAP kinases ERK1 and ERK2: Pleiotropic enzymes in a ubiquitous signaling network. Adv. Cancer Res. 63:93-116 (1994).
21. K. Sikora. Developing a global strategy for cancer. Eur. J. Cancer 35:1870-1877 (1999).
22. J. Bos. Ras oncogenes in human cancer: a review. Cancer Res. 49:4682-4689 (1989).
23. D. Y. Mitchell, J. M. Reid, R. E. Parchment, M. B. Meyer, J. S. Leopold, R. Herrera, J. R. Piens, L. M. Bruzek, L. J. Hanson, K. Van Becelaere, T. Carlson, C. Packard, A. A. Adjei, and P. M. LoRusso. Pharmacokinetics (PK) and pharmacodynamics (PD) of the oral MEK inhibitor. CI-1040. following multiple dose administration to patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. 21:81 (2002).
24. R. Seger and E. Krebs. The MAPK signaling cascade. FASEB 9:726-735 (1995).
25. R. Seger, N. Ahn, J. Posada, E. Munar, A. Jensen, J. Cooper, M. Cobb, and E. Krebs. Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. J. Biol. Chem. 267:14373-14381 (1992).
26. C. Tournier, C. Dong, T. Turner, S. Jones, R. Flavell, and R. Davis. MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes Dev. 15:1419-1426 (2001).
27. J. S. Sebolt-Leopold. Development of anticancer drugs targeting the MAP kinase pathway. Oncog. 19:6594-6599 (2000).
28. J. Uusitalo, J. Jalonen, and O. Pelkonen. Identification of N+-and O-glucuronides of finrozole by LC/TOF. LC/MS/MS and LC/ PB/MS. Adv. Mass Spec. 15:693-694 (2001).
29. T. C. Sarich and T. Adams. P Stephen, P. Petricca, G. Giorgio, and J.M. Wright. Inhibition of isoniazid-induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor. J. Pharm. Exp. Ther 289:695-702 (1999).
30. Y. Ono, X. Wu, A. Noda, H. Noda, and T. Yoshitani. Participation of P450-dependent oxidation of isoniazid in isonicotinic acid formation in rat liver. Biol. Pharm. Bull. 21:421-425 (1998).