CAY17c is an inhibitor of bromodomain-containing protein 4 (BRD4; IC₅₀= 0.71 µM), as well as class I histone deacetylases (HDACs; IC₅₀s = 0.046, 0.058, 0.075, and 0.167 µM for HDAC1, -2, -3, and -8, respectively) and class IIb HDACs (IC₅₀s = 0.073 and 0.923 µM for HDAC6 and HDAC10, respectively).¹It is selective for these enzymes over BRD2, -3, and -T (IC₅₀s = >20 µM for all), as well as over HDAC4, -5, -7, -9, and -11 (IC₅₀s = >10 µM for all). CAY17c inhibits the proliferation of HCT116, SW620, and DLD-1 colorectal cancer cells (IC₅₀s = 0.45, 1.78, and 2.11 µM, respectively), as well as induces apoptosis and autophagy in HCT116 cells. It reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 15 and 30 mg/kg.

1.Pan, Z., Li, X., Wang, Y., et al.Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cellsJ. Med. Chem.63(7)3678-3700(2020)