HDAC-IN-53 is an orally active, selective inhibitor of HDAC1-3, with IC50 values of 47 nM, 125 nM, and 450 nM, respectively. It exhibits no inhibitory effects on class II HDACs (HDAC4, 5, 6, 7, 9; IC50 >10 μM). The compound induces caspase-dependent apoptosis and significantly hampers the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice with MC38 colon cancer [1].

HDAC1:47 nM, HDAC2:125 nM, HDAC3:450 nM, HDAC4:>10 μM, HDAC5:>10 μM, HDAC6:>10 μM, HDAC7:>10 μM, HDAC8:>10 μM, HDAC9:>10 μM

HDAC-IN-53 (Compound 19h) exhibits robust antiproliferative activity against a panel of cancer cell lines, such as MC38 (IC50 = 0.66 μM) and HCT116 cells (IC50 = 0.56 μM) [1]. At concentrations ranging from 0.1 to 1 μM over 24 hours, HDAC-IN-53 induces G0/G1 cell cycle arrest in MC38 cells and G2/M cell cycle arrest in HCT116 cells [1]. Additionally, the same treatment with HDAC-IN-53 dose-dependently upregulates the expression of cleaved caspase-3 and cleaved PARP [1].

HDAC-IN-53, administered orally at doses of 60 or 120 mg/kg once daily for 15 days, exhibited antitumor activity through both direct inhibition of tumor growth and indirect immune cell-mediated antitumor effects[1]. The pharmacokinetic parameters of HDAC-IN-53 in mice are reported as follows[1]: after intravenous (IV) administration at 5 mg/kg, the time to maximum concentration (Tmax) is 0.42 hours, with a maximum concentration (Cmax) of 8129 ng/mL. The area under the curve (AUC0-t) is 5864 ng/mL∗h, and the half-life (t1/2) is 0.85 hours. In contrast, after oral administration (PO) at 20 mg/kg, Tmax is 0.42 hours, Cmax is 9558 ng/mL, AUC0-t is 15278 ng/mL∗h, t1/2 is 2.49 hours, and the bioavailability (F%) is 65.1%.