Toxicity and toxicokinetics of the cyclin-dependent kinase inhibitor AG-024322 in cynomolgus monkeys following intravenous infusion (original) (raw)

References

  1. Arguello F, Alexander M, Sterry JA, Gabriela T, Smith EM, Kalavar NT, Greene JF, Koss W, Morgan CD, Stinson SF, Siford TJ, Alvord WG, Klabansky RL, Sausville EA (1998) Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts. Blood 91(7):2482–2490
    PubMed CAS Google Scholar
  2. Baughn LB, Di Liberto M, Wu K, Toogood PL, Louie T, Gottschalk R, Niesvizky R, Cho H, Ely S, Moore MAS, Chen-Kiang S (2006) A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6. Cancer Res 66(15):7661–7667
    Article PubMed CAS Google Scholar
  3. Fink JR, LeBien TW (2001) Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors. Exp Hematol 29:490–498
    Article PubMed CAS Google Scholar
  4. Fischer PM, Gianella-Borradori A (2003) CDK inhibitors in clinical development for the treatment of cancer. Expert Opin Investig Drugs 12(6):955–970
    Article PubMed CAS Google Scholar
  5. Fry DW, Bedford DC, Harvey PH, Fritsch A, Keller PR, Wu Z, Dobrusin E, Leopold WR, Fattaey A, Garrett MD (2001) Cell cycle and biochemical effects of PD 0183812, a potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. J Biol Chem 276(20):16617–16623
    Article PubMed CAS Google Scholar
  6. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL (2004) Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 3(11):1427–1437
    PubMed CAS Google Scholar
  7. Furukawa Y, Kikuchi J, Nakamura M, Iwase S, Yamada H, Matsuda M (2000) Lineage-specific regulation of cell cycle control gene expression during haematopoetic cell differentiation. Br J Haematol 110:663–673
    Article PubMed CAS Google Scholar
  8. Garrett MD, Fattaey A (1999) CDK inhibition and cancer therapy. Curr Opin Genet Dev 9:104–111
    Article PubMed CAS Google Scholar
  9. Jessen BA, Lee L, Koudriakova T, Haines M, Lundgren K, Price S, Nonomiya J, Lewis C, Stevens GJ (2007) Peripheral white blood cell toxicity induced by broad spectrum cyclin-dependent kinase inhibitors. J Appl Toxicol 27:133–142
    Article PubMed CAS Google Scholar
  10. Kim JH, Kang MJ, Park CU, Kwak HJ, Hwang Y, Koh GY (1999) Amplified CDK2 and cdc2 activities in primary colorectal carcinoma. Cancer 85(3):546–553
    Article PubMed CAS Google Scholar
  11. Ko TC, Bresnahan WA, Thompson EA (1997) Intestinal cell cycle regulation. Prog Cell Cycle Res 3:43–52
    PubMed CAS Google Scholar
  12. O’Dwyer PJ, LoRussso P, DeMichele A, Gupta V, Barbi A, Dials H, Chen I, Courtney R, Wilner K, Schwartz GK (2007). Phase I dose escalation trial of a daily oral CDK 4/6 inhibitor PD-0332991. J Clin Oncol. 2007 ASCO annual meeting proceed part 1. vol 25. no 18S (abstract 3550)
  13. Ramiro-Ibanez F, Trajkovic D, Jessen B (2005) Gastric and pancreatic lesions in rats treated with a pan-CDK inhibitor. Toxicol Pathol 33:784–791
    Article PubMed CAS Google Scholar
  14. Rixe O, Fojo T (2007) Is cell death a critical end point for anticancer therapies or is cytostasis sufficient? Clin Cancer Res 13(24):7280–7287
    Article PubMed CAS Google Scholar
  15. Shapiro GI (2004) Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin Cancer Res (suppl) 10:4270s–4275s
    Article CAS Google Scholar
  16. Sherr CJ (1995) D-type cyclins. Trends Biol Sci 20:187–190
    Article CAS Google Scholar
  17. Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677
    Article PubMed CAS Google Scholar
  18. Stadler WM, Vogelzang NJ, Amato R, Sosman J, Taber D, Liebowitz D, Vokes EE (2000) Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II consortium study. J Clin Oncol 18(2):371–375
    PubMed CAS Google Scholar
  19. Tan AR, Headlee D, Messman R, Sausville EA, Arbuck SG, Murgo AJ, Melillo G, Zhai S, Figg WD, Swain SM, Senderowicz AM (2002) Phase I clinical and pharmacokinetic study of flavopiridol administered as a daily 1-hour infusion in patients with advanced neoplasms. J Clin Oncol 20(19):4074–4082
    Article PubMed CAS Google Scholar
  20. Tetsu O, McCormick F (2003) Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 3:233–245
    Article PubMed CAS Google Scholar
  21. Zhang CC, Kephart S, McAlpine I, Nonomiya J, Higgins J, Arango ME, Yan Z, Knighton D, Ferre RA, Tikhe J, Verkhivker G, Xu M, Romines W, Palmer C, Park J, Reich S, Chong W, Li L, Los G, Lewis C (2005) AG-024322 is a potent and selective multi-targeted CDK inhibitor with broad spectrum anti-proliferative activity. Proc Am Assoc Cancer Res 46 (abstract 4415)
  22. Zhang CC, Troche G, Yan Z, Arango ME, Higgins J, Romero D, Kephart S, McAlpine I, Koudriakova T, Skaptason J, Nonomiya J, Knighton D, Ferre RA, Tikhe J, Verkhivker G, Xu M, Romines W, Palmer C, Park J, Reich S, Los G, Lewis C (2005) AG-024322 is a multi-targeted CDK inhibitor with potent antitumor activity in vivo. Proc Am Assoc Cancer Res 46 (abstract 4413)
  23. Zhang T, Nanney LB, Luongo C, Lamps L, Heppner KJ, DuBois RN, Beauchamp RD (1997) Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in intestinal adenomas from multiple intestinal neoplasia (Min) mice and human familial adenomatous polyposis patients. Cancer Res 57:169–175
    PubMed CAS Google Scholar

Download references