Zabadinostat

CXD101 is a potent, selective and orally active class I HDAC inhibitor with IC₅₀s of 63 nM, 570 nM and 550 nM for HDAC1, HDAC2 and HDAC3, respectively. CXD101 has no activity against HDAC class II. CXD101 has antitumor activity^[1][2]. In Vitro: CXD101 has been tested in vitro in colon, lung, non-Hodgkin lymphoma, and myeloma cell lines with IC₅₀s ranged from 0.2 to 15 μM^[2]. In Vivo: CXD101 substantially reduces tumor size in murine xenograft lung (A549a) and colon (HT29) models at a dose of 50 mg/kg. Tumor reductions are found to be associated with increased histone acetylation and decreased HDAC enzyme activity^[2].
For CXD101, after oral dosing in murine and canine models, peak plasma concentrations (C_max) are reached 1 to 2 hours after the dose and terminal half‐lives are 6 hours and 8 hours, respectively. After murine oral [¹⁴C]-CXD101 at a dose of 1.6 mg/kg (4 μmol/kg), tissue radioactivity peaked 3 to 6 hours after the dose and declined slowly thereafter with CXD101‐related material still present in tissue 21 days after the dose^[2].