Background:

LY2157299 is a potent small-molecule antagonist that specifically inhibits Transforming Growth Factor-β receptor I (TβRI). LY2157299 is now under phase II clinical evaluation of its anti-carcinoma activity against hepatocellular carcinoma and glioblastoma¹.

LY2157299 has been shown to inhibit β1-integrin activation and block the invasion and migration of hepatocellular cancer cells. In addition, multiple studies have revealed LY2157299 blocked the CTGF production and inhibited neoangiogenesis resulting suppression of hepatocellular carcinoma growth¹.

LY2157299 has been reported to decrease phosphorylated Smad2 and Smad3 expression and inhibit the tumor growth in both human anaplastic carcinoma lung cell (Calu6) or human carcinoma breast cell (MX1) xenografted nude mice².

参考文献:
1. Giannelli G1, Villa E, Lahn M.Transforming Growth Factor-β as a Therapeutic Target in Hepatocellular Carcinoma. Cancer Res. 2014 Apr 1;74(7):1890-4. doi: 10.1158/0008-5472.CAN-14-0243. Epub 2014 Mar 17.
2. Bueno L1, de Alwis DP, Pitou C, Yingling J, Lahn M, Glatt S, Trocóniz IFSemi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-beta kinase antagonist, in mice. Eur J Cancer. 2008 Jan;44(1):142-50.