Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs

Toxicology

Volumn 289, Issue 2-3, 2011, Pages 141-150

  Johnson, William D ^a   Muzzio, Miguel ^a   Detrisac, Carol J ^b   Kapetanovic, Izet M ^c   Kopelovich, Levy ^a   McCormick, David L ^a  

^a IIT RESEARCH INSTITUTE   (United States)

^b Charles River Pathology Associates   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Chemopreventive agent; Chemotherapeutic agent; CP 31398; N' 2 2 (4 Methoxyphenyl)ethenyl 4 quinazolinyl N,N dimethyl 1,3 propanediamine dihydrochloride; P53

Indexed keywords

4 (3 DIMETHYLAMINOPROPYLAMINO) 2 (4 METHOXYSTYRYL)QUINAZOLINE; DRUG METABOLITE; PROTEIN P53;

ADRENAL GLAND; ANEMIA; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BLOOD CLOTTING DISORDER; BONE MARROW; CENTRAL NERVOUS SYSTEM; CHRONIC TOXICITY; CONTROLLED STUDY; DOG; DRUG DOSE COMPARISON; DRUG EXPOSURE; DRUG FATALITY; DRUG MEGADOSE; ERYTHROCYTE; FEMALE; HEART; INFLAMMATION; KIDNEY; LIVER; LIVER ISCHEMIA; LIVER NECROSIS; LIVER TOXICITY; LOW DRUG DOSE; LUNG; MALE; MAXIMUM TOLERATED DOSE; MICROSCOPY; NEPHROTOXICITY; NONHUMAN; OVARY; PRIORITY JOURNAL; RAT; SKELETAL MUSCLE; SPLEEN; THYMUS; VOMITING; WEIGHT REDUCTION;

ADMINISTRATION, ORAL; ANIMALS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; EXCIPIENTS; FEMALE; KIDNEY; MALE; METABOLOME; PROTEIN CONFORMATION; PROTEIN STABILITY; PYRIMIDINES; RATS; TUMOR SUPPRESSOR PROTEIN P53;

CANIS FAMILIARIS; RATTUS;

EID: 80052739172     PISSN: 0300483X     EISSN: 18793185     Source Type: Journal    
DOI: 10.1016/j.tox.2011.08.009     Document Type: Article

References (24)

1. Brown C.J., Cheok C.F., Verma C.S., Lane D.P. Reactivation of p53: from peptides to small molecules. Trends Pharmacol. Sci. 2011, 32:53-62.
2. Brown C.J., Lain S., Verma C.S., Fersht A.R., Lane D.P. Awakening guardian angels: drugging the p53 pathway. Nat. Rev. Cancer 2009, 9:862-873.
3. Cheok C.F., Verma C.S., Baselga J., Lane D.P. Translating p53 into the clinic. Nat. Rev. Clin. Oncol. 2011, 8:25-37.
4. Demma J.J., Wong S., Maxwell E., Dasmahapatra B. CP-31398 restores DNA-binding activity to mutant p53 in vitro but does not affect p53 homologs p63 and p73. J. Biol. Chem. 2004, 279:45887-45896.
5. Foster B.S., Coffey H.A., Morin M.J., Rastinejad F. Pharmacological rescue of mutant p53 conformation and function. Science 1999, 286:2507-2510.
6. Greenblatt M.S., Bennett W.P., Hollstein M., Harris C.C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994, 54:4855-4878.
7. Harris M.P., Sutjipto S., Wills K.N., Hancock W., Cornell D., Johnson D.E., Gregory R.J., Shepard H.M., Maneval D.C. Adenovirus-mediated p53 gene transfer inhibits growth of human tumor cells expressing mutant p53 protein. Cancer Gene Ther. 1996, 3:121-130.
8. Harris S.L., Levine A.J. The p53 pathway: positive and negative feedback loops. Oncogene 2005, 24:2899-2908.
9. Hollstein M., Sidransky D., Vogelstein B., Harris C.C. p53 mutations in human cancers. Science 1991, 253:49-53.
10. Horowitz J. Adenovirus-mediated p53 gene therapy: overview of preclinical studies and potential clinical applications. Curr. Opin. Mol. Ther. 1999, 1:500-509.
11. Joerger A.C., Fersht A.R. Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene 2007, 26:2226-2242.
12. Kern S.E., Kinzler K.W., Bruskin A., Jarosz D., Friendman P., Prives C., Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science 1991, 252:1708-1711.
13. Kim S.H., Dass C.R. p53-targeted cancer pharmacotherapy: move towards small molecule compounds. J. Pharm. Pharmacol. 2011, 63:605-610.
14. Levine A.J. p53, the cellular gatekeeper for growth and division. Cell 1997, 88:323-331.
15. Luu Y., Bush J., Cheung K.J., Li G. The p53 stabilizing compound CP-31398 induces apoptosis by activating the intrinsic Bax/mitochondrial/caspase-9 pathway. Exp. Cell Res. 2002, 276:214-222.
16. Molchadsky A., Rivlin N., Brosh R., Rotter V., Sarig R. p53 is balancing development, differentiation and de-differentiation to assure cancer prevention. Carcinogenesis 2010, 31:1501-1508.
17. Muzzio M., Huang Z., Johnson W.D., McCormick D.L., Kapetanovic I.M. Determinatino and stability of CP-31398 in plasma from experimental animals by LC-MS/MS. J. Pharm. Biomed. Anal. 2011, 56:809-814.
18. Rao C.V., Steele V.E., Swamy M.V., Patlolla J.M., Guruswamy S., Kopelovich L. Inhibition of azoxymethane-induced colorectal cancer by CP-31398, a TP53 modulator, alone or in combination with low doses of Celecoxib in male F34 rats. Cancer Res. 2009, 69:8175-8182.
19. Rao C.V., Swamy M.V., Patlolla J.M., Kopelovich L. Suppression of familial adenomatous polyposis by CP-31398, a TP53 modulator in APCmin/+ mice. Cancer Res. 2008, 68:7670-7675.
20. Roh J.L., Kang S.K., Minn I., Califano J.A., Sidransky D., Koch W.M. p53-Reactivating small molecules induce apoptosis and enhance chemotherapic cytotoxicity in head and neck squamous cell carcinoma. Oral Oncol. 2011, 47:8-15.
21. Takimoto R., Wang W., Dicker D.T., Rastinejad F., Lyssikatos J., El-Deiry W.S. The mutant p53-conformation modifying drug, CP-31398, can induce apoptosis in human cancer cells and can stabilize wild-type p53 protein. Cancer Biol. Ther. 2002, 1:47-55.
22. Tang X., Zhu Y., Han L., Kim A.L., Kopelovich L., Bickers D.R., Athar M. CP-31398 restores mutant p53 tumor suppressor function and inhibits UVB-induced skin carcinogenesis in mice. J. Clin. Invest. 2007, 117:3753-3764.
23. Wang W., Rastinejad F., El-Deiry W.S. Restoring p53-dependent tumor suppression. Cancer Biol. Ther. 2003, 2:S55-S63.
24. Xu J., Timares L., Heilpern C., Weng Z., Li C., Xu H., Pressey J.G., Elmets C.A., Kopelvich L., Athar M. Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing reactive oxygen species-dependent apoptosis. Cancer Res. 2010, 70:6566-6576.