CDKs, a crucial cell cycle regulators family, have been investigated in the phosphorylation of C-terminal domain. The terminal domain, however, contains repeating peptide (Tyr-ser-pro-thr-ser-pro-ser ) sequence. 2-anilino-4-(heteroaryl)-pyrimidine kinase inhibitor compound was modified in various derives .There are 1,3,4,6,7,14 selective inhibit aurora kinase. Compound 1 had no effect on the level of histone H2AX phosphoryltion. all the compound were able to induce caspase-3/7 response in A2780,NCI-460,MES-SA,and HT-29.However,compound 14 unable to holt the cell cycle on A2780 and WI38. Compounds with the transcriptional inhibitor phenotype predominantly inhibit CDK7 and CDK9 and show varying selectivity toward other CDKs, in particular CDK2 and CDK4. Derivatives 9 and 10 are highly inhibit the expression of CDK9. Antiproliferative activity revealed that the ser-2 and ser-5 were phosphorylated less than control.p53 was unregulated due to inhibition by compound 14. after 24h both A2780 and WI-38 cells revealed the low-expression of antiapoptotic proteins(XIAP,Mcl-1,Survivin),however, the observation of PARP depression occurred in A2780 cell line but not in WI-38 cell line. The reason might be refered to antiapoptoic proteins act as a minor role in untransformed cells. The vivo experiments was performed demonstrated that animal models had well tolerance for compound 14 and signicant increases survival rate and antitumor activity. Regardless of any specific chromosomal aberration, in vitro, PHA-793887 wascytotoxic for leukemic cell lines, with IC50 ranging from 0.3 to 7M (mean: 2.9M). Contrastively, the drug was not cytotoxic for CD34+ hematopoietic stem cells or nstimulated peripheral blood mononuclear cells at these doses. PHA-793887showed very high activity against leukemia cell lines in colony assays, with an IC50
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