文摘
A series of aminoacyl-triazine derivatives based upon the pan-PI3K inhibitor ZSTK474 were identified as potent and isoform-selective inhibitors of PI3K尾. The compounds showed selectivity based upon stereochemistry with l-amino acyl derivatives preferring PI3K尾, while their d-congeners favored PI3K未. The mechanistic basis of this inhibition was studied using site-directed mutants. One Asp residue, D862, was identified as a critical participant in binding to the PI3K尾-selective inhibitors, distinguishing this class from other reported PI3K尾-selective inhibitors. The compounds show strong inhibition of cellular Akt phosphorylation and growth of PTEN-deficient MD-MBA-468 cells.
Keywords:
PI3 kinase; p110尾; ZSTK474; cancer