The cellular phenotype of AZ703, a novel selective imidazo[1,2-a]pyridine cyclin-dependent kinase inhibitor

Molecular Cancer Therapeutics

Volumn 5, Issue 3, 2006, Pages 655-664

  Byth, Kate F ^a   Geh, Catherine ^a   Forder, Cheryl L ^a   Oakes, Sandra E ^a   Thomas, Andrew P ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AZ 703; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; FLAVOPIRIDOL; IMIDAZO[1,2 A]PYRIDINE DERIVATIVE; PROTEIN KINASE; ROSCOVITINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CARCINOMA; CANCER CELL CULTURE; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CELL PROLIFERATION; COLON CARCINOMA; CONTROLLED STUDY; DRUG POTENCY; DRUG STRUCTURE; ENZYME ASSAY; ENZYME INHIBITION; HELA CELL; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; LUNG CARCINOMA; OVARY CARCINOMA; PHENOTYPE; PRIORITY JOURNAL; PROSTATE CARCINOMA; PROTEIN PHOSPHORYLATION; SQUAMOUS CELL CARCINOMA; UTERINE CERVIX CARCINOMA;

APOPTOSIS; CDC2 PROTEIN KINASE; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE 2; HUMANS; IMIDAZOLES; NEOPLASMS; PHENOTYPE; PHOSPHORYLATION; PYRIDINES;

EID: 33645471100     PISSN: 15357163     EISSN: None     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-05-0205     Document Type: Article

References (41)

1. Sherr CJ. Cancer cell cycles. Science 1996;274:1672-7.
2. Senderowicz AM, Sausville EA. Preclinical and clinical development of cyclin-dependent kinase modulators. J Natl Cancer Inst 2000;92:376-87.
3. Shapiro GI, Harper JW. Anticancer drug targets: cell cycle and checkpoint control. J Clin Invest 1999;104:1645-53.
4. 1. Cell 1999;98: 859-69.
5. Krek W, Xu G, Livingston DM. Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint. Cell 1995;83:1149-58.
6. Chen Y-NP, Sharma SK, Ramsey TM, et al. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists. Proc Natl Acad Sci U S A 1999;96:4325-9.
7. Hinds PW. Cdk2 dethroned as master of S phase entry. Cancer Cell 2003;3:305-7.
8. Tetsu O, McCormick F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 2003;3:233-45.
9. Sausville EA, Arbuck SG, Messmann R, et al. Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms. J Clin Oncol 2001;19:2319-33.
10. Shapiro GI, Supko JG, Patterson A, et al. A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res 2001;7: 1590-9.
11. Schwartz GK, Ilson D, Saltz L, et al. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol 2001;19:1985-92.
12. Stadler WM, Vogelzang NJ, Amato R, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II Consortium study. J Clin Oncol 2000;18:371-5.
13. McClue SJ, Blake D, Clarke R, et al. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int J Cancer 2002;102:463-8.
14. Kim KS, Kimball SD, Misra RN, et al. Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X-ray crystallographic analysis, and biological activities. J Med Chem 2002;45:3905-27.
15. Bramson HN, Corona J, Davis ST, et al. Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. J Med Chem 2001;44:4339-58.
16. Anderson M, Beattie JF, Breault GA, et al. Imidazo[1,2-a]pyridines: a potent and selective class of cyclin-dependent kinase inhibitors identified through structure-based hybridization. Bioorg Med Chem Lett 2003;13: 3021-6.
17. Byth KF, Culshaw JD, Green S, Oakes SE, Thomas AP. Imidazo[1,2-a]pyridines 2: SAR and optimization of a potent and selective class of cyclin-dependent kinase inhibitors. Bioorg Med Chem Lett 2004;14: 2245-8.
18. Kitagawa M, Higashi H, Jung H-K, et al. The consensus motif for phosphorylation by cyclin D1-4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J 1996;15:7060-9.
19. 1-S cyclin-dependent kinases. J Biol Chem 1997;272:12738-46.
20. Connell-Crowley L, Harper JW, Goodrich DW. Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell 1997;8:287-301.
21. Morisaki H, Fujimoto A, Ando A, Nagata Y, Ikeda K, Nakanishi M. Cell cycle-dependent phosphorylation of p27 cyclin-dependent kinase (Cdk) inhibitor by cyclin E/Cdk2. Biochem Biophys Res Commun 1997;240: 386-90.
22. Sheaff RJ, Groudine M, Gordon M, Roberts JM, Clurman BE. Cyclin E-CDK2 is a regulator of p27Kip1. Genes Dev 1997;11:1464-78.
23. Matranga CB, Shapiro GI. Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase. Cancer Res 2002;62:1707-17.
24. Davies TG, Pratt DJ, Endicott JA, Johnson LN, Noble MEM. Structure-based design of cyclin-dependent kinase inhibitors. Pharmacol Ther 2002;93:125-33.
25. Shapiro GI. Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin Cancer Res 2004;10:4270-5s.
26. Cai D, Byth KF, Shapiro GI. AZ703, an imidazo[1-2a]pyridine inhibitor of cyclin-dependent kinases 1 and 2, induces E2F-1-dependent apoptosis enhanced by depletion of cyclin dependent kinase 9. Cancer Res 2006;66:435-44.
27. Kim KS, Sack JS, Tokarski JS, et al. Thio-and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects. J Med Chem 2000;43:4126-34.
28. Zhang G-J, Safran M, Wei W, et al. Bioluminescent imaging of Cdk2 inhibition in vivo. Nat Med 2004;10:643-8.
29. o-1 transition mediated by a Skp2-independent ubiquitination pathway. J Biol Chem 2001; 276: 48937-43.
30. 1 and S phase. Nature 2001; 413: 323-7.
31. Foster JS, Fernando RI, Ishida N, Nakayama KI, Wimalasena J. Estrogens down-regulate p27kip1 in breast cancer cells through nuclear export mediated by the ERK pathway. J Biol Chem 2003;278:41355-66.
32. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 1999;13:1501-12.
33. Harper JW, Adams PD. Cyclin-dependent kinases. Chem Rev 2001; 101:2511-26.
34. Coverley D, Laman H, Laskey RA. Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nat Cell Biol 2002;4:523-8.
35. 2 phase roles for Cdk2 revealed by inducible expression of a dominant-negative mutant in human cells. Mol Cell Biol 2001;21:2755-66.
36. Castedo M, Perfettini J-L, Roumier T, Kroemer G. Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe. Cell Death Differ 2002;9:1287-93.
37. Sausville EA. Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol Med 2002;8:S32-7.
38. Mitra J, Enders GH. Cyclin A/Cdk2 complexes regulate activation of Cdk1 and Cdc25 phosphatases in human cells. Oncogene 2004;23: 3361-7.
39. O'Connor DS, Wall NR, Porter ACG, Altieri DC. A p34cdc2 survival checkpoint in cancer. Cancer Cell 2002;2:43-54.
40. Benson C, Raynaud F, O'Donnell A, et al. Pharmacokinetics (PK) of the oral cyclin dependent kinase inhibitor CYC202 (R-roscovitine) in patients with cancer. Proc Am Assoc Cancer Res 2002;43:273.
41. Pevarello P, Villa M. Cyclin-dependent kinase inhibitors: a survey of the recent patent literature. Expert Opin Ther Patents 2005;15: 675-703.