Author/Authors :
Xiaodong Lin، نويسنده , , Jeremy M. Murray، نويسنده , , Alice C. Rico، نويسنده , , Michael X. Wang، نويسنده , , Daniel T. Chu، نويسنده , , Yasheen Zhou، نويسنده , , Merci Del Rosario، نويسنده , , Susan Kaufman، نويسنده , , Sylvia Ma، نويسنده , , Eric Fang، نويسنده , , Kenneth Crawford، نويسنده , , A.B. Jefferson، نويسنده ,
Abstract :
A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC50 values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed.
Keywords :
Protein Kinase B/Akt , kinase inhibitor , Substituted pyrimidine , cancer
