Author/Authors :
Jinjun Liu، نويسنده , , Apostolos Dermatakis، نويسنده , , Christine Lukacs، نويسنده , , Fred Konzelmann، نويسنده , , Yi Chen، نويسنده , , Ursula Kammlott، نويسنده , , Wanda Depinto، نويسنده , , Hong Yang، نويسنده , , Xuefeng Yin، نويسنده , , Yingsi Chen، نويسنده , , Andy Schutt، نويسنده , , Mary Ellen Simcox، نويسنده , , Kin-Chun Luk، نويسنده ,
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.
