Disease relevance of LY317615

• LY317615 significantly decreased plasma VEGF levels in mice bearing SW2 SCLC and Caki-1 renal cell carcinoma compared to control plasma concentrations beginning 5-7 days after initiating therapy [1].
• Enzastaurin (LY317615), a protein kinase Cbeta inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines [2].

High impact information on LY317615

• PKCbeta promoter activity and PKCbetaII mRNA expression in HCT116 cells are inhibited by the selective PKCbeta inhibitor LY317615 and by U0126, demonstrating autoregulation of PKCbetaII expression [3].
• LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice [1].
• Mice bearing these human tumor xenografts were treated orally twice daily with the PKCbeta inhibitor, LY317615 (days 14-30 for SW2 and HCT116, and days 21-39 for Caki-1) [1].
• Plasma VEGF was a weak marker of response to LY317615, and plasma bFGF and TGFbeta were not markers of LY317615 activity [1].
• As shown by CD31 immunohistochemical staining, LY317615 decreased intratumoral vessel density by nearly 40% in all three tumors [1].

Gene context of LY317615

• Plasma VEGF levels in mice bearing HCT116 xenografts were not altered by LY317615 treatment and plasma bFGF and TGF-beta were not altered by LY317615 in any of the animals [1].

References