858474-14-3

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 SKOV3_TR and OVCAR-8_TR cells to paclitaxel . NSC 23925 reverses P-gp efflux, increasing the intracellular accumulation of P-gp substrates, including calcein AM in multidrug-resistant SKOV3_TR and OVCAR-8_TR 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.

This molecule shows an ibility to inhibit plasma membrane glycoprotein 1 (Pgp1) in order to counter and even reverse multi-drug resistance (MDR1) in patients diagnosed with cancer.

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[1] ZHENFENG DUAN  Francis J H  Edwin Choy. NSC23925, identified in a high-throughput cell-based screen, reverses multidrug resistance.[J]. PLoS ONE, 2009: e7415. DOI: 10.1371/journal.pone.0007415
[2] XIAOQIAN YANG . NSC23925 prevents the emergence of multidrug resistance in ovarian cancer in vitro and in vivo[J]. Gynecologic oncology, 2015, 137 1: Pages 134-142. DOI: 10.1016/j.ygyno.2015.02.002