Carbonic anhydrase-IN-35 is a selective inhibitor of carbonic anhydrase (CA), demonstrating potent inhibition of tumor-associated hCA IX (Ki= 0.6 nM) and hCA XII (Ki= 2.2 nM). It induces autophagic apoptosis in MCF-7 cells by increasing Bax, decreasing Bcl-2, and downregulating CDK4/6. Carbonic anhydrase-IN-35 exhibits significant cytotoxicity against MCF-7 (IC50= 0.3975 μM normoxia / 0.6575 μM hypoxia), MCF-7-ADR (IC50= 0.3975 μM normoxia / 4.488 μM hypoxia), MDA-MB-231, and 4T1 breast cancer cells. This compound is applicable in breast cancer research.

CA IX (human):0.6 nM (Ki)

Carbonic anhydrase-IN-35 (Compound 10a) is a potent inhibitor of tumor-associated human carbonic anhydrase isozymes IX (K i = 0.6 nM), XII (K i = 2.2 nM), I (K i = 6183 nM), and II (K i = 12.7 nM). It exhibits significant cytotoxicity against MCF-7 cells under normoxic conditions (IC 50 = 0.3975 μM) and hypoxic conditions (IC 50 = 0.6575 μM). Against MCF-7-ADR breast cancer cells, it shows strong cytotoxic effects in normoxia (IC 50 = 0.3975 μM) and hypoxia (IC 50 = 4.488 μM). The compound also demonstrates potent antiproliferative activity in MDA-MB-231 triple-negative breast cancer cells (IC 50 = 1.9 μM) and in 4T1 triple-negative breast cancer cells (IC 50 = 2.38 μM). After 24 hours in MCF-7 breast cancer cells, Carbonic anhydrase-IN-35 increases the expression of the pro-apoptotic factor Bax and downregulates anti-apoptotic factors Bcl-2 and CDK4/6.