TW-37 binds to the BH3 binding groove in Bcl-2 protein competing with BH3 peptides derived from Bid, Bim, and Bad proteins. TW-37 binds to Bcl-2 with a K(i) value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities.TW-37 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner. TW-37 has an IC50 of 1.1 µmol/L for primary human endothelial cells and averaged 0.3 µmol/L for head and neck cancer cells (OSCC3,UM-SCC-1, and UMSCC-74A). The combination of TW-37 and cisplatin showed enhanced cytotoxic effects for endothelial cells and HNSCC in vitro, compared with single drug treatment.

2. Zeitlin BD, et al. Cancer Res, 2006, 66(17), 8698-8706.