tcsc0132 Enzastaurin

Enzastaurin is a potent PKCβ selective inhibitor with IC₅₀ of 6 nM, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε.

IC50 & Target: IC50: 6 nM (PKCβ)

In Vitro: Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrates an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 leads 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 induces the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreases the mRNA levels and surface expression of CD44^[1].

Enzastaurin 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^[3].

In Vivo: Treatment of xenografts with Enzastaurin and radiation produces greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponds to delayed tumor growth^[2].