NSC 23925 is a non-substrate inhibitor of P-glycoprotein (P-gp). It selectively reverses multidrug resistance mediated by P-gp over resistance mediated by multidrug resistance-associated protein 1 (MRP1/ABCC1) or breast cancer resistance protein (BCRP/ABCG2). It resensitizes paclitaxel-resistant SKOV3TR and OVCAR-8TR cells to paclitaxel . NSC 23925 reverses P-gp efflux, increasing the intracellular accumulation of P-gp substrates, including calcein AM in multidrug-resistant SKOV3TR and OVCAR-8TR cells. It prevents paclitaxel-induced overexpression of the P-gp gene MDR1 and P-gp protein level increases in OVCAR-8 cells. It also prevents the development of paclitaxel-induced multidrug resistance in a SKOV3 mouse xenograft model when administered at a dose of 50 mg/kg per day in combination with paclitaxel.
