Một người luôn có cái nhìn tổng thể, bao quát chứ không chú ý đến tiểu tiết. without permission from the American Chemical Society. has the potential to provide an effective strategy for the treatment of cancer. modulates other steps during transcription. By comparison with a previously published structure of CDK9/cyclin T/human immunodeficiency virus TAT we find that the CDK9 αC-helix has a degree of conformational variability that has the potential to be exploited for inhibitor design.There is no corresponding record for this reference.Wang, Shudong; Meades, Christopher; Wood, Gavin; Osnowski, Andrew; Anderson, Sian; Yuill, Rhoda; Thomas, Mark; Mezna, Mokdad; Jackson, Wayne; Midgley, Carol; Griffiths, Gary; Fleming, Ian; Green, Simon; McNae, Iain; Wu, Su-Ying; McInnes, Campbell; Zheleva, Daniella; Walkinshaw, Malcolm D.; Fischer, Peter M.Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analog program was initiated. While most known inhibitors display broad selectivity toward multiple CDKs, recent work highlights CDK9 as the crit. use and an effective strategy to specifically control malignant cell proliferation has yet to be established. The package has been ported to all the major platforms under both Unix and VMS. Enzymol.
of CDK2 tyrosine phosphorylation. It has greatest activity against CDK2/cyclin E, CDK7/cyclin H, and CDK9/cyclin T. Seliciclib induces apoptosis from all phases of the cell cycle in tumor cell lines, reduces tumor growth in xenografts in nude mice and is currently in phase II clin. Among the serine-threonine kinases, p38, Rho-kinase, cyclin-dependent kinases, and Chk1 have been targeted with productive results for inflammation and cancer. Recent developments have focused on providing tools for expert users, with customisable key bindings, extensions and an extensive scripting interface. Comparative Structural and Functional Studies of 4-(Thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 Inhibitors Suggest the Basis for Isotype Selectivity. properties and a novel binding mode, whereby a bridging interaction via a water mol. In U2OS cells, combined depletion affected RNA polymerase II expression and phosphorylation, causing decreased expression of the antiapoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis (XIAP), effects usually mediated by inhibition of the transcriptional cdk9.
Here, the authors discuss recent findings provided by structural biologists that may allow further development of highly specific inhibitors of CDK9 toward applications in cancer therapy.
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