product name Sotrastaurin
Description: Sotrastaurin, also known as AEB-071, is an orally bioavailable, potent and selective pan-PKC inhibitor, mostly for PKCθ with Ki of 0.22 nM in a cell-free assay; it is inactive to PKCζ. Sotrastaurin inhibits both T- and B-cell activations via PKC theta and beta isozymes, respectively. Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents.
References: J Pharmacol Exp Ther. 2009 Sep;330(3):792-801; Cancer Res. 2011 Apr 1;71(7):2643-53; Transpl Int. 2010 May 1;23(5):543-52.
438.48
Formula
C25H22N6O2
CAS No.
425637-18-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 87 mg/mL (198.4 mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL (4.6 mM)
Solubility (In vivo)
2% DMSO+30% PEG 300+ddH2O: 10 mg/mL
Synonyms
AEB071
other peoduct :
| In Vitro |
In vitro activity: Sotrastaurin (< 10μM) treatment effectively abrogated at low nanomolar concentration markers of early T-cell activation, such as interleukin-2 secretion and CD25 expression, in primary human and mouse T cells. Sotrastaurin (200 nM) inhibits the CD3/CD28 antibody- and alloantigen-induced T-cell proliferation responses in the absence of nonspecific antiproliferative effects. Sotrastaurin (<3 μM) markedly inhibits lymphocyte function-associated antigen-1-mediated T-cell adhesion. Sotrastaurin(< 20 μM) selectively impair the proliferation of CD79 mutant ABC DLBCL cell lines, correlating with decreased NF-κB signaling avctivity. AEB071 at concentration of 5 μM induces G1 arrest and/or cell death in CD79 mutant cells. Kinase Assay: Cell Assay: ABE071 is a potent inhibitor of novel and classical PKC isoforms. Through the inhibition of PKC, AEB071 can depress the activation and proliferation of T-cell and decrease the production of cytokine.ABE071 can also suppress the NK cell activity. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression. |
|---|---|
| In Vivo | Sotrastaurin (80 mg/kg) results in significant inhibition of in vivo tumor growth in a subcutaneous TMD8 xenograft model in SCID. Sotrastaurin orally administrated at 10 mg/kg and 30 mg/kg b.i.d. show a dose-dependent immunosuppressive effect leading to pronounced prolongation of heart allograft survival in rats. |
| Animal model | Male Wistar/F rats |
| Formulation & Dosage | Dissolved in saline; 10, 30 mg/kg twice daily; oral gavage |
| References | J Pharmacol Exp Ther. 2009 Sep;330(3):792-801; Cancer Res. 2011 Apr 1;71(7):2643-53; Transpl Int. 2010 May 1;23(5):543-52. |
