Sotrastaurin

Sotrastaurin is a protein kinase C (PKC) inhibitor that displays immunosuppressive activity, blocking T cell activation through the disruption of downstream NF-kappaB signaling. In cell-free assays, sotrastaurin was reported to inhibit PKCalpha, betaI, delta, epsilon, eta, and theta with Ki values of 0.95, 0.64, 2.1, 3.2, 1.8, and 0.22 nM, respectively. Sotrastaurin can prevent the production of various cytokines by activated T cells, macrophages, and keratinocytes in vitro and has been shown to inhibit an acute allergic contact dermatitis response in rats when dosed orally at 30 mg. However, clinical investigation of sotrastaurin for its potential to prevent renal transplant rejection was halted during phase II testing due to high incidence of rejection. Sotrastaurin is also reported to activate Wnt/beta-catenin signaling via the inhibition of glycogen synthase kinase 3 (IC50s = 229 and 172 nM for alpha and beta isoforms, respectively), which is essential for embryogenesis and adult stem cell maintenance.Formal Name: 3-(1H-indol-3-yl)-4-[2-(4-methyl-1-piperazinyl)-4-quinazolinyl]-1H-pyrrole-2,5-dione. CAS Number: 425637-18-9. Synonyms: AEB071. Molecular Formula: C25H22N6O2. Formula Weight: 438.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 10 mg/ml, Ethanol: 5 mg/ml. lambdamax: 246, 438 nm. SMILES: CN(CC1)CCN1C2=NC3=CC=CC=C3C(C(C(N4)=O)=C(C5=CNC6=C5C=CC=C6)C4=O)=N2. InChi Code: InChI=1S/C25H22N6O2/c1-30-10-12-31(13-11-30)25-27-19-9-5-3-7-16(19)22(28-25)21-20(23(32)29-24(21)33)17-14-26-18-8-4-2-6-15(17)18/h2-9,14,26H,10-13H2,1H3,(H,29,32,33). InChi Key: OAVGBZOFDPFGPJ-UHFFFAOYSA-N.