HDAC-IN-71 (Compound 17q), a potent HDAC inhibitor, exhibits IC 50 values of 12.6 nM for HDAC1, 14.1 nM for HDAC2, 20 nM for HDAC3, 3 nM for HDAC6, and 72 nM for HDAC10. This compound induces apoptosis and is utilized in cancer research [1].

HDAC1:12.6 nM, HDAC2:14.1 nM, HDAC3:20 nM

HDAC-IN-71 effectively inhibits colony formation of DU145 cells in a dose-dependent manner at concentrations ranging from 0 to 1.6 μM over 24 hours, with complete inhibition occurring at 3.2 μM. Over a 72-hour period, it arrests the cells in the G2/M phase and induces apoptosis in a concentration-dependent manner. In a Cell Migration Assay, using DU145 cells with concentrations of 0 to 1.6 μM for 12 hours, HDAC-IN-71 inhibits cancer cell migration. Cell Cycle Analysis shows that DU145 cells are arrested in the G2/M phase with concentrations of 0 to 1.6 μM for 72 hours. Western Blot Analysis demonstrates histone acetylation induction and HDAC6 expression inhibition in DU145 cells treated with 0.8, 1.6, and 3.2 μM for 24 hours.

HDAC-IN-71 was administered orally at doses of 100 and 200 mg/kg daily for a duration of 40 days in Balb/c nude mice, resulting in tumor growth inhibition (TGI) of 50.92% and 68.00% respectively [1]. Pharmacokinetic parameters indicated that the AUC 0-∞ for I.V. (2 mg/kg) and P.O. (10 mg/kg) were 1633.35 and 3799.46 (h ng/mL), half-lives (T 1/2) were 3.12 and 2.87 (h), clearance (CL) was 1.57 (L/h/kg), and volume of distribution (V) was 4.63 (L/kg). The maximum concentrations (C max) reached were 851.5 and 774.0 (ng/mL), with a bioavailability (F) of 46.52%. The results demonstrate a significant suppression of prostate cancer (PCa) tumor growth.