Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.

摘要: Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, concentrations which vary throughout progression As central mediators growth, CDKs potential targets for inhibitory molecules that would allow disruption cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several 2,6,9-trisubstituted purine derivatives solved crystal structure one these compounds, H717, complex human CDK2 at 2.6 A resolution. The orientation C2-p-diaminocyclohexyl portion inhibitor is strikingly from those similar moieties other related complexes. N9-cyclopentyl ring fully occupies a space enzyme otherwise empty, while C6-N-aminobenzyl substituent points out ATP-binding site. provides basis further development more potent drugs.