Enzastaurin (LY317615) (C09-0880-576)

InformationEnzastaurin (LY317615) Enzastaurin (LY317615) is a potent PKCβ selective inhibitor with IC50 of 6 nM in cell-free assays, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε. Phase 3.In vitroEnzastaurin application results in a marked dose-dependent inhibition of growth in all MM cell lines investigated, including MM.1S, MM.1R, RPMI 8226 (RPMI), RPMI-Dox40 (Dox40), NCI-H929, KMS-11, OPM-2, and U266, with IC50 from 0.6-1.6 μM. Enzastaurin direct impacts human tumor cells, inducing apoptosis and suppressing proliferation in cultured tumor cells. Enzastaurin also suppresses the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308 while having no direct effect on VEGFR phosphorylation. Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrated an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 led to increased levels of β-catenin total protein and β-catenin-mediated transcription. Blocking of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin induced the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44.In vivoTreatment of xenografts with Enzastaurin and radiation produced greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponded to delayed tumor growth.Cell Datacell lines：Human mammary epithelial cells (HMEC), human foreskin fibroblasts (MRHF) cellsConcentrations：0.3-4 μMIncubation Time：72 hoursPowder Purity:≥98%. Specification: 10mM in DMSO Molecular Formula: C32H29N5O2 Molecular Weight: 515.61