3,5,6-Trisubstituted naphthostyrils as CDK2 inhibitors.

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Liu JJ, Dermatakis A, Lukacs C, Konzelmann F, Chen Y, Kammlott U, Depinto W, Yang H, Yin X, Chen Y, Schutt A, Simcox ME, Luk KC

3,5,6-Trisubstituted naphthostyrils as CDK2 inhibitors.

Bioorg Med Chem Lett. 2003 Aug 4;13(15):2465-8.

PubMed ID

12852944 [ View in PubMed

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Abstract

A novel class of 3,5,6-trisubstituted naphthostyril analogues was designed and synthesized to study the structure-activity relationship for inhibition of cyclin-dependent kinase 2 (CDK2). These compounds, particularly molecules with side-chain modifications providing additional hydrogen bonding capability, were demonstrated to be potent CDK2 inhibitors with cellular activities consistent with CDK2 inhibition. These molecules inhibited tumor cell proliferation and G1-S and G2-M cell-cycle progression in vitro. The X-ray crystal structure of a 2-aminoethyleneamine derivative bound to CDK2, refined to 2.5A resolution, is presented.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
5-[(2-AMINOETHYL)AMINO]-6-FLUORO-3-(1H-PYRROL-2-YL)BENZO[CD]INDOL-2(1H)-ONE	Cyclin-dependent kinase 2	IC 50 (nM)	12	7.5	22	Details