in HCT-116 tumor–bearing nude mice: 10, 30, or 100 mg/kg

KD5170 is a potent HDAC inhibitor in vitro, with an IC50 of 0.045 ± 0.007 μmol/L in the HeLa cell nuclear extract screening assay. To define the isoform selectivity of KD5170, biochemical assays with individual recombinant human enzymes were done. Among class I enzymes, KD5170 most potently inhibited HDAC1 [IC50, 0.020 ± 0.004 μmol/L (SE); n = 5] and HDAC3 [IC50, 0.075 ± 0.01 μmol/L (SE); n = 5]. KD5170 was a significantly less potent inhibitor of HDAC2 [IC50, 2.0 ± 0.12 μmol/L (SE); n = 5], which is surprising because these two isoforms have the highest degree of amino acid homology (93%) among the class I enzymes. KD5170 also potently inhibited HDAC4 and HDAC6, with IC50 values of 0.026 μmol/L (SE, ±0.003 μmol/L; n = 5) and 0.014 μmol/L (SE, ±0.002 μmol/L; n = 5), respectively.