TW9 is a dual inhibitor of bromodomain 2 (BD2) in bromodomain-containing protein 4 (BRD4) and histone deacetylase 1 (HDAC1; IC50s = 0.074 and 0.29 µM, respectively).1 It is selective for BD2 over BD1 in BRD4 (IC50 = 0.72 µM) and for HDAC1 over HDAC2 (IC50 = 2.5 µM). TW9 (50 nM) induces apoptosis in, and inhibits proliferation of, MIA PaCa-2 pancreatic cancer cells. It induces cell cycle arrest at the G1 phase in HPAC pancreatic cancer cells when used at a concentration of 2 µM. TW9 acts synergistically with gemcitabine to reduce the viability of HPAC cells.
1.Zhang, X., Zegar, T., Weiser, T., et al.Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinomaInt. J. Cancer147(10)2847-2861(2020)