HDAC-IN-84 (compound 4a) is a potent HDAC inhibitor with IC50 values of 0.0045, 0.015, 0.013, 0.038, 5.8, and 26 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC11, respectively. It effectively inhibits the proliferation of leukemia cells without causing toxicity.

HDAC11:26 μM

HDAC-IN-84 (95min) inhibits HDAC1, HDAC2, HDAC3, HDAC4, HDAC6, HDAC8, and HDAC11 with IC50 values of 0.0045, 0.015, 0.013, >100, 0.038, 5.8, and 26 μM, respectively [1]. HDAC-IN-84 (0.005-25 μM, 72 h) suppresses HL60, HPBALL, and K562 cells with IC50 values of 76.8, 110.6, and 180.8 nM, respectively [1]. Treatment with HDAC-IN-84 (0.25 μM, 48 h) significantly acetylates α-tubulin and enhances PARP protein cleavage by HDAC6 [1]. This compound (0.25 μM, 48 h) promotes apoptosis in HL60 cells [1]. It also induces cell cycle arrest in HL60 cells at doses of 0.15-0.2 μM over 24 hours [1]. Furthermore, HDAC-IN-84 shows excellent stability in human plasma at 37°C following 24-hour incubation at concentrations of 2.5, 50 nM, and 1 μM [1]. In plasma protein binding studies, HDAC-IN-84 (2.5, 50 nM, 1 μM, 48 h) averages a binding rate of 99.0% across observed concentrations, with no concentration dependence [1]. Additionally, HDAC-IN-84 (0-1 μM) inhibits MV4-11 cell growth with an IC50 of 0.036 μM, demonstrating over seven times the potency of Vorinostat [1]. HDAC-IN-84 (0-10 μM, 72 h) and Vorinostat also affect C1498 cell growth in a concentration-dependent manner, with IC50 values of 0.425 and 1.06 μM, respectively.

HDAC-IN-84 administered at a dosage of 10 mg/kg via intraperitoneal injection (i.p.) once daily for 14 days suppresses the growth of MV4-11 and C1498 cells in a preclinical NSG mouse model of leukemia [1]. The compound has a half-life of 0.35 hours in three C57BL/6 mice [1]. Additionally, HDAC-IN-84 at 20 mg/kg i.p., administered daily for 21 days, results in a significantly lower leukemia burden in an allograft leukemia model, without notable differences in body weight [1].