Staurosporine

Staurosporine (antibiotic AM-2282 or STS) is a therapeutic agent that inhibits tumor cell growth by inducing cell death via intrinsic apoptotic pathways. Staurosporine is a prototypical ATP-competitive kinase inhibitor in that it binds to many kinases with high affinity, though with little selectivity. Staurosporine also inhibits a variety of other protein kinases, including PKA, PKG, phosphorylase kinase, S6 kinase, MLCK, CAM PKII, cdc2, v-Src, Lyn, c-Fgr and Syk with IC50 values of 15 nM, 18 nM, 3 nM, 5 nM, 21 nM, 20 nM, 9 nM, 6 nM, 20 nM, 2 nM and 16 nM respectively. Staurosporine induces apoptosis of human foreskin fibroblasts AG-1518, depending on the lysosomal cathepsins D mediated cytochrome c release and caspase activation. Moreover, Staurosporine triggers a novel intrinsic apoptosis pathway, relying on the activation of caspase-9 in the absence of Apaf-1.