6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, N-[4-[[(2-aminophenyl)amino]carbonyl]phenyl]-4-(4-chlorophenyl)-2,3,9-trimethyl-, (6S)-

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 adenocarcinoma Int. J. Cancer 147(10),2847-2861(2020).