HDAC-IN-89 is an inhibitor of HDAC1 (IC50: 0.95 nM), HDAC2 (IC50: 0.86 nM), HDAC3 (IC50: 1.06 nM), and HDAC8 (IC50: 4.24 nM). It can disrupt the cell cycle and induce apoptosis. Additionally, HDAC-IN-89 exhibits antitumor activity.

HDAC1:0.95 nM

HDAC-IN-89 (Compound 12) exhibits cytotoxicity against NCI-H1975 (IC 50: 0.57 μM) and HT-29 (IC 50: 0.17 μM) cancer cell lines, while showing significantly reduced toxicity in normal WRL-68 (IC 50: 2.6 μM) and HEK293 (IC 50: 1.0 μM) cells. At concentrations of 250 nM to 1 μM for 48 hours, HDAC-IN-89 induces cell cycle arrest at the G0/G1 phase in HT-29 cells and significantly promotes both early and late apoptosis. Additionally, HDAC-IN-89 demonstrates minimal inhibition (21%) of the h ERG potassium channel at 0-40 μM, indicating a low risk of cardiotoxicity.

HDAC-IN-89 (Compound 12) administered intraperitoneally at doses of 2.2 mg/kg and 11 mg/kg every three days for 21 days inhibits tumor growth by 63.5% and 87.9% in a mouse NCI-H1975 xenograft model, while exhibiting low toxicity.