AG-346

AG-346 is a small molecule pyrrolo[2,3-d]pyrimidine derivative developed as a microtubule-targeting antitumor agent. It acts by binding to the colchicine site of tubulin, leading to microtubule depolymerization and inhibition of cell division. Developed through a collaboration between Duquesne University and the University of Texas Health Science Center at San Antonio, AG-346 served as a lead compound in structure-activity relationship (SAR) studies to identify more potent analogs like AG473. It has demonstrated activity against human melanoma cancer cell lines (e.g., MDA-MB-435) and has the potential to circumvent drug resistance mechanisms such as P-glycoprotein (Pgp) expression and βIII-tubulin isotypes. Preclinical studies were underway as of 2017 to further evaluate its potential as an in vivo antitumor agent.