Therapeutics: Histone deacetylase (HDAC); HDAC1

In vitro and mouse studies identified prodrug inhibitors of class I HDACs that could help treat cancer. In enzyme inhibition assays, two prodrugs of cyclic depsipeptide analogs of Istodax romidepsin inhibited class I HDACs more potently than Istodax, with IC50 values for HDAC1 of 15.8 and 2.2 nM. In human cancer cell lines, each prodrug inhibited proliferation with IC50 values of 5-11 nM. In a xenograft mouse model of prostate cancer, IV administration of one prodrug decreased tumor growth compared with vehicle. Next steps could include testing the prodrugs in additional cancer models...