Sotrastaurin | CAS:425637-18-9

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Name:Sotrastaurin; AEB071
Cat. No. :CS-0090
CAS No. :425637-18-9
Formula:C25H22N6O2
M. Wt. : 438.48
Solubility:10 mM in DMSO

Sotrastaurin is a potent pan-PKC inhibitor, with Kis of 0.22 nM, 0.64nM, 0.95 nM, 1.8 nM, 2.1 nM and 3.2 nM for PKCθ, PKCβ, PKCα, PKCη, PKCδ and PKCε, respectively.IC50 & Target: IC50: 0.22 nM (PKCθ), 0.64 nM (PKCβ), 0.95 nM (PKCα), 1.8 nM (PKCη), 2.1 nM (PKCδ), 3.2 nM (PKCε)[1]In Vitro: In cell-free kinase assays Sotrastaurin (AEB071) inhibits PKC, with Ki values in the subnanomolar to low nanomolar range. When Sotrastaurin is tested on a selected panel of kinases, the only enzyme on which Sotrastaurin displays an IC50value below 1 μM is glycogen synthase kinase 3β[1]. Sotrastaurin (AEB071) inhibits p-MARCKS, a PKC substrate, and pS6 in all the cell lines, independently of the mutational status. There is a slight inhibition of pERK at lower doses also in the GNA11 mutant cells, but not in the WT cells at any concentrations. This is consistent with previous reports indicating that Sotrastaurin inhibits ERK1/2 phosphorylation in GNAQ mutant cell lines[2].In Vivo: The combination therapy results in a significantly enhanced reduction in tumor volume when compared to either Sotrastaurin (AEB071) or BYL719 alone (p=0.049 vs. BYL719 and p=0.022 vs. Sotrastaurin at day 26). There is even a greater effect when compared to vehicle control (p=0.016)[2]. Sotrastaurin (STN) treatment of liver donors and orthotopic liver transplantation (OLT) recipients (Gr.I) or of OLT recipients alone (Gr.II) prolongs animal survival, as 9 out of 10 rats in Gr. I, and 6 out of 6 rats in Gr.II survive >14 days. In contrast, only 4 out of 10 control OLT recipients remain alive at day 14 (p[3].

Musi E, et al. The phosphoinositide 3-kinase α selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells. Mol Cancer Ther. 2014 May;13(5):1044-53. Kamo N, et al. Sotrastaurin, a protein kinase C inhibitor, ameliorates ischemia and reperfusion injury in rat orthotopic liver transplantation. Am J Transplant. 2011 Nov;11(11):2499-507. Evenou JP, et al. The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation. J Pharmacol Exp Ther. 2009 Sep;330(3):792-801.