NSC 23925B

NSC 23925B is a P-glycoprotein (P-gp) inhibitor and the most bioactive isomer of NSC23925, capable of reversing and preventing P-gp-mediated multidrug resistance in cancer cells. It exhibits weak inhibition against most CYP450 enzymes (IC50 > 10 μM) but shows moderate inhibition of CYP2B6 and CYP2D6, with IC50 values of 8.589 μM and 1.407 μM, respectively. NSC 23925B is useful for studying multidrug-resistant cancers.

NSC 23925B effectively reverses Pgp-mediated multidrug resistance (MDR) in human breast cancer and colon cancer MDR cell lines. Additionally, NSC 23925B inhibits the development of anticancer drug resistance mediated by Pgp in ovarian cancer cells and osteosarcoma cells.

NSC 23925B, administered in single doses via intraperitoneal or intravenous injection at 2.50-93.75 mg/kg, exhibits favorable pharmacokinetic characteristics in male BALB/c mice, such as high bioavailability and detectable plasma concentration within 24 hours, with limited toxicity. The maximum tolerated dose in male mice via intraperitoneal injection is at least 68.80 mg/kg, while for both male and female mice via intravenous injection, it is 24.70 mg/kg. In male Sprague-Dawley rats, NSC 23925B, given in single doses of 2.50-47.20 mg/kg via intraperitoneal or intravenous injection, also shows favorable pharmacokinetics, including high bioavailability, detectable plasma levels within 24 hours, and limited toxicity. The maximum tolerated dose in male rats via intraperitoneal injection is at least 33.10 mg/kg, and via intravenous injection is at least 38.80 mg/kg.