HDAC3 inhibitor 4i is a potent, selective HDAC3 inhibitor with IC50 of 14 nM, shows 121-fold selectivity over HDAC1 (IC50=1983 nM) and HDAC2 (IC50=1696 nM).
HDAC3 inhibitor 4i shows no activity against other HDACs such as HDAC8 (IC50 = 10,744 nM), HDAC6 (IC50 = 25,930 nM), HDAC4 (IC50 > 20,000 nM) and HDAC5 (IC50 > 20,000 nM).
HDAC3 inhibitor 4i exhibits a minimum of 17.5-fold HDAC3 inhibitory potency than the reference HDAC3 inhibitor UF010 (IC50=256.7 nM).
HDAC3 inhibitor 4i exhibits selectivity toward different subtypes of breast cancer cell lines (4T1, IC50=0.55 uM) over normal human cell lines including normal breast cell line MCF-10A (IC50>200 uM).
HDAC3 inhibitor 4i induced significant apoptosis and causes G2/M phase cell cycle arrest in TNBC cells.
HDAC3 inhibitor 4i demonstrates potential in overcoming the oxaliplatin resistance in the TNBC cell line MDA-MB-231.
HDAC3 inhibitor 4i (5 mg/kg, and 15 mg/kg) inhibits tumor growth in the 4T1-Luc tumor-bearing mouse model.