Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development

Annals of Pharmacotherapy

Volumn 36, Issue 5, 2002, Pages 905-911

  Zhai, Suoping ^a   Senderowicz, Adrian M ^b   Sausville, Edward A ^a   Figg, William D ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Cyclin dependent kinase; Flavopiridol

Indexed keywords

ANTIDIARRHEAL AGENT; ANTINEOPLASTIC AGENT; COLESTYRAMINE; CYCLIN DEPENDENT KINASE INHIBITOR; DOCETAXEL; FLAVOPIRIDOL; PACLITAXEL;

ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; CANCER; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; CONTINUOUS INFUSION; DIARRHEA; DISTRIBUTION VOLUME; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG RESPONSE; DRUG STRUCTURE; FATIGUE; HUMAN; MAXIMUM TOLERATED DOSE; NEUTROPENIA; NONHUMAN; PRIORITY JOURNAL; REVIEW; THROMBOSIS; TUMOR XENOGRAFT;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS, PHASE I; CLINICAL TRIALS, PHASE II; COLONIC NEOPLASMS; CYCLIN-DEPENDENT KINASES; DIARRHEA; DRUG EVALUATION, PRECLINICAL; DRUG THERAPY, COMBINATION; FATIGUE; FLAVONOIDS; HUMANS; INFUSION PUMPS; KIDNEY NEOPLASMS; LYMPHOMA, NON-HODGKIN; NEOPLASMS; NEUTROPENIA; PIPERIDINES;

EID: 0036093681     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1A162     Document Type: Review

References (46)

1. Cancer cell cycles
2. Principles of CDK regulation
3. Cyclin-dependent kinases: Engines, clocks, and microprocessors
4. The cell cycle
5. Cell cycle control and cancer
6. CDK inhibitors in development and cancer
7. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasmas
8. A. Cyclin-dependent kinases: Initial approaches to exploit a novel therapeutic target
9. Preclinical and clinical development of cyclin-dependent kinase modulators
10. Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells
11. Downregulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol
12. Potent inhibition of CDK2 kinase activity by the flavonoid L86-8275
13. Inhibition of CDK2, CDK4 and CDK7 by flavopiridol and structure analogs
14. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase
15. Alteration of phosphorylation state of p34cdc2 kinase by flavone L86-8275 in breast carcinoma cells
16. Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: The importance of sequence of administration
17. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol
18. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis
19. Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia
20. Bcl-2 independence of flavopiridolinduced apoptosis. Mitochondrial depolarization in the absence of cytochrome c release
21. Flavopiridol binds to duplex DNA
22. Overexpression of cyclin DI correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck
23. Overexpression of cyclin DI in human pancreatic carcinoma is associated with poor prognosis
24. High level expression of p27(kipl) and cyclin D1 in some human breast cancer cells: Inverse correlation between the expression of p27(kipl) and degree of malignancy in human breast and colorectal cancers
25. Flavopiridol, a potent kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes
26. Cell cycle-dependent induction of apoptosis by the antitumor drug flavopiridol in endothelial cells
27. Antitumor activity of flavone L86-8275
28. Flavopiridol (L86-8275): Selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells
29. Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275
30. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts
31. Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver
32. In vitro glucuronidation of flavopiridol (NSC649890) by human liver microsomes (abstract)
33. In vitro glucuronidation of the cyclin-dependent kinase inhibitor flavopiridol by rat and human liver microsomes: Involvement of UDP-glucuronosyltransferases I A1 and I A9
34. Phase I clinical and pharmacokinetic trial of flavopiridol
35. Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase (CDK) inhibitor flavopiridol
36. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma
37. Pharmacokinetics of flavopiridol I hour infusion in patients with refractory neoplasms (abstract)
38. Flavopiridol metabolism in cancer patients is associated with occurrence of diarrhea
39. Possible mechanisms of diarrheal side effects associated with the use of a novel chemotherapeutic agent, flavopiridol
40. A Phase I clinical trial of 1-hour infusion of flavopiridol, a novel cyclin-depedent kinase inhibitor, in patients with advanced neoplasms
41. Flavopiridol enhances the biological effects of paclitaxel: A Phase I trial in patients with advanced solid tumors
42. Phase I trial of docetaxel and flavopiridol in metastatic breast cancer: Preliminary results
43. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: A University of Chicago Phase 11 consortium study
44. A Phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small-cell lung cancer
45. A randomized phase III trial of four chemotherapy regimens in advanced non-small cell lung cancer (NSCLC)