QW-5-70 is a colchicine binding site inhibitor (CBSI) with SPR KD of 10.8 uM for colchicine site on tubulin, inhibits tubulin polymerization, disrupts microtubule networks, and induces mitotic arrest, circumvents P-gp-associated resistance.
QW-5-70 maintained low-nanomolar activity and remained effective in vincristine-resistant BE2C/VCR and paclitaxel-resistant PC-3/TxR cells (K-N-BE(2)-C, IC50=1.0 uM).
Unlike vincristine and paclitaxel, the activity and intracellular accumulation of QW-5-70 were unaffected by pharmacologic or genetic inhibition of P-gp, indicating effective circumvention of efflux-mediated resistance.
QW-5-70 significantly reduced colony formation and impaired migration in both parental and resistant cancer cells and induced G2–M cell-cycle arrest and mitochondrial apoptosis.
QW-5-70 significantly suppressed tumor growth in drug-resistant PC-3/TxR and BE2C/VCR xenografts, with modest weight loss and no evident histopathology in the major organs.