Polmacoxib

Polmacoxib is an inhibitor of cyclooxygenase 2 (COX-2) and the carbonic anhydrase subtypes I (CAI) and CAII. It inhibits COX-2 in the absence of carbonic anhydrase II with an IC50 value of 40 nM, which increases by approximately 4- and 17-fold in the presence of a CAII at a molar ratio of 1:1 and 1:5, respectively. It also inhibits CAI and CAII (IC50s = 210 and 95 nM, respectively). Polmacoxib prevents >95 and 90% of prostaglandin E2 (PGE2) production in HCA-7 and HT-29 human colon cancer cells, respectively, using concentrations of 0.01 and 0.001 ug/ml. It inhibits polyp formation in a transgenic mouse model of intestinal polyp formation and tumor growth in human colorectal carcinoma mouse xenograft models when used at a dose of 7 mg/kg. The inhibition of COX-2 and CAII by polmacoxib has the potential for fewer serious systemic adverse effects, including cardiovascular events associated with COX-2 selective inhibitors such as celecoxib . Formulations containing polmacoxib have been used in the treatment of osteoarthritis.