| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T32612 | ||||
| Target Name | Cyclin-dependent kinase | ||||
| Target Type | Discontinued |
||||
| Drug Potency against Target | Flavopiridol | Drug Info | IC50 = 3 nM | [537564] | |
| Action against Disease Model | Flavopiridol | Treatment of the cells (JVM-2, I83CLL, WSU-CLL) with flavopiridol (100 nmol/L to 400 nmol/L) led to a marked dose- and time-dependent inhibition of cell growth and survival as determined using trypan blue exclusion. Morphologic analysis showed characteristic apoptotic changes such as chromatin condensation and fragmentation, membrane blebbing, and formation of apoptotic bodies. Furthermore, quantitative assessment of apoptosis-associated DNA strand breaks by in situ TdT labeling showed that a significant n uMber of flavopiridol-treated cells underwent apoptosis. These cellular effects were associated with a significant decrease in bcl-2 expression as observed by Northern and Western blotting. The results showed that flavopiridol downregulates bcl-2 mRNA and bcl-2 protein expression within 24 hours. | [553260] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | p27 de?ciency did not alter breast cancer rate in either male or female Wnt-1 mice.However,we did ?nd p27-/2 females had reduced levels of ser uM progesterone (P) and increased variability in estradiol (E),which could have affected their cancer susceptibility To equalize hormone levels, an additional cohort of Wnt-1 female mice was ovariectomized and implanted with slow release pellets of E and P.Although this treatment did not alter the breast cancer rate, it did accelerate the development of pituitary and gastric t uMors in p27-/- mice. | [553260] | |||
| References | |||||
| Ref 553260 | The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines. Blood. 1997 Dec 1;90(11):4307-12. | ||||
| Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
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