CUDC-101 is a multi-target inhibitor, combining functional groups of potent inhibitors of human epidermal growth factor receptor (HER) kinases and histone deacetylases (HDACs). It potently blocks the receptor tyrosine kinases EGFR (aka HER1) and HER2 (IC50s = 2.4 and 16.4 nM, respectively). CUDC-101 also inhibits the activity of class I and class II HDACs at nanomolar concentrations (e.g., IC50s = 4.5, 12.6, 13.2, and 11.4 nM for HDAC1, 2, 4, and 5, respectively). It has only weak effects on over 60 other kinases when tested at 5 μM. CUDC-101 prevents the growth of a wide range of cancer cell lines in vitro, and slows tumor growth or induces tumor regression through cancer cell apoptosis in xenograft models. In cancer cells that have acquired resistance to single-target EGFR inhibitors, CUDC-101 blocks proliferation and reduces cell migration.
