metatinib tromethamine (BMS-794833)

Recently, several TKIs, for instance regorafenib and cabozantinib, have showed clinical interest in treating osteosarcoma and target both vascular endothelial growth factor receptor (VEGFR) and mesenchymal epithelial transition factor (c-MET)...More importantly, BMS-794833 and anlotinib exerted synergistic therapeutic effects against osteosarcoma in vivo. Altogether, this study reveals a new (VEGFR)-targeting drug that can be combined with anlotinib for the treatment of osteosarcoma, which provides an important theoretical basis for overcoming anlotinib resistance.

BMS-794833, a multitargeted compound, was identified as a potent inhibitor of TAM polarization...The effect of BMS-794833 was independent of its primary targets (MET and VEGFR2) but was dependent on its effect on multiple signaling pathways, including focal adhesion kinases, SRC family kinases, STAT3, and p38 MAP kinases. Collectively, these findings underline the efficacy of polypharmacological strategies in reprogramming complex signaling cascades activated during TAM polarization.

Metatinib administration of 200 mg/day was well tolerated, safe, and effective. The MTD was 200 mg/day, which should be recommended in further investigations.