HDAC-IN-91 is a multi-target inhibitor affecting HDAC [HDAC1 (IC50= 134.22 nM), HDAC2 (IC50= 66.29 nM)], carbonic anhydrase [CA IX (KI= 72.03 nM), XII (KI= 50.76 nM)], and tubulin polymerization (IC50= 2.56 μM). It inhibits PARP1 and increases the Bax/Bcl-2 ratio. The compound causes cell cycle arrest at the G2/M phase and triggers apoptosis through mitochondrial pathways. By inhibiting tubulin polymerization, HDAC-IN-91 exhibits potent cytotoxic activity. This compound is applicable in research on breast cancer, colorectal cancer, cervical cancer, and lung cancer.

HDAC1:134.22 nM

HDAC-IN-91 (Compounds 6e) demonstrates cytotoxicity against MCF7, Hela, HCT116, and A549 cells, with IC 50 values of 1.40 μM, 2.22 μM, 1.57 μM, and 2.54 μM, respectively. It displays significant inhibitory activity against HDAC subtypes 3, 4, 6, and 8, with an IC 50 range of 100-900 nM. At a concentration of 1.40 μM for 48 hours, HDAC-IN-91 impedes the growth of MCF-7 cells by disrupting mitosis and ultimately inducing apoptosis. Additionally, it increases the Bax/Bcl-2 ratio and levels of caspase-9 and caspase-7 in MCF-7 cells to trigger apoptosis. HDAC-IN-91 also exhibits potential PARP1 inhibitory activity in MCF-7 cells.