Sotrastaurin | PKC inhibitor

Sotrastaurin (425637-18-9) is a highly selective and potent (IC₅₀’s for PKC isotypes: α = 2.1 nM, ß1 = 2.0 nM, δ = 1.3 nM, ε = 6.2 nM, η = 6.1 nM, Θ = 1.0 nM) pan-PKC inhibitor.¹ Potent immunomodulatory agent that inhibits early T-cell activation and displays potential for the prevention of transplant rejection and the treatment of inflammatory diseases.^2,3 Sotrastaurin has anticancer activity in various cancer models including breast⁴, CLL⁵, ocular melanoma⁶, and B-cell lymphoma⁷.

References/Citations:

1. Wagner et al. (2009), Discovery of 3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071),a Potent and Selective Inhibitor of Protein Kinase C Isotypes; J. Med. Chem. 52 6193
2. Manicassamy (2009), Sotrastaurin, a protein kinase C inhibitor for the prevention of transplant rejection and treatment of psoriasis; Curr. Opin. Investig. Drugs 10 1225
3. Matz et al. (2011), Evaluation of the novel protein kinase C inhibitor sotrastaurin as immunosuppressive therapy after renal transplantation; Expert Opin. Drug Metab. Toxicol. 7 103
4. Byerly et al. (2016), PRKCQ promotes oncogenic growth and anoikis resistance of a subset of triple-negative breast cancer cells; Breast Cancer Res. 18 95
5. El-Gamal et al. (2014), PKC-beta as a therapeutic target in CLL: PKC inhibitor AEB071 demonstrates preclinical activity in CLL; Blood 124 1481
6. Wu et al. (2012), Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-kappaB pathways; Mol. Cancer Ther. 11 1905
7. Naylor et al. (2011), Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas; Cancer Res. 71 2643