compound 14a

Compound 14a is a novel nitric oxide (NO)-releasing estra-1,3,5,16-tetraene analog designed to combat multidrug resistance in liver cancer. It functions as a dual inhibitor of the Epidermal Growth Factor Receptor (EGFR) and Multidrug Resistance-associated Protein 2 (MRP2). By releasing nitric oxide and inhibiting these targets, it demonstrates potent anti-proliferative activity against both sensitive (HepG2) and resistant (HepG2-R) hepatocellular carcinoma cell lines. Mechanistically, it reduces EGFR phosphorylation, downregulates MRP2 expression, and induces cell cycle arrest in the S phase. It was developed as an improvement over previous estratriene analogs by incorporating a ∆-16 unsaturation in the steroid scaffold, which significantly enhances its anti-proliferative potency.

Other names

(R)-isomer of nitric oxide-releasing estra-1,3,5,16-tetraene analogNO-∆-16-CIEA 14a