BO-264 is a transforming acidic coiled-coil containing protein 3 (TACC3) inhibitor.1 It binds to TACC3 in thermal shift and drug affinity responsive target stability (DARTS) assays and inhibits the growth of JIMT-1, HCC1954, MDA-MB-231, MDA-MB-436, and CAL-51 cancer cells (IC50s = 0.19, 0.16, 0.12, 0.13, and 0.36 ?M, respectively). BO-264 is cytotoxic to RT4 cells that endogenously express TACC3-FGFR3 fusion proteins (IC50 = 3.66 ?M). It induces mitotic arrest, apoptosis, and aberrant spindle formation and reduces centrosomal localization of TACC3 in JIMT-1 cells. BO-264 (25 mg/kg) reduces tumor volume and increases median survival in an EMT6 mouse xenograft model.
1.Akbulut, O., Lengerli, D., Saatci, O., et al.A highly potent TACC3 inhibitor as a novel anticancer drug candidateMol. Cancer Ther.19(6)1243-1254(2020)