QW-296 is a novel microtubule destabilizer with little susceptible to transporter-mediated drug resistance, disturbs the microtubule dynamics at the nanomolar concentration in A375 and B16F10 melanoma cells.
QW-296 binds to colchicine-binding site on tubulin protein.
QW-296 significantly inhibited A375 and B16F10 cell proliferation, induced G2/M cell cycle arrest and led to apoptosis and cell death.
Systemic administration of QW-296 loaded nanoparticles into C57/BL6 albino mice bearing lung metastatic melanoma at the dose of 20 mg/kg 4 times a week for 1.5 weeks resulted in significant tumor regression and prolonged mouse median survival without significant change in mouse body weight.
The combination of QW-296 and MDB5 exhibited stronger anticancer activity toward DU145-TXR and PC3-TXR cells and suppressed taxane-resistant (TXR) prostate cancer colony formation when compared with single-drug treatment.