[CAS NO. 1096708-71-2]  Tovorafenib (MLN2480)

MLN2480 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preclinical cancer models at concentrations that are tolerated in vivo.It is found to activate phosphorylated MEK at very low concentrations, but inhibits this same activity at higher concentrations. The inhibitory effects of MLN-2480 are found to vary across models and genetic contexts.In vitro analysis of this drug combination of MLN2480 and TAK-733(an investigational allosteric MEK kinase inhibitor) in cell proliferation assays demonstrates synergistic activity .In addition, western blot analysis demonstrates the effect of MLN2480 in reversing feedback activation of MEK in response to TAK-733, leading to more concerted MAPK pathway inhibition.MLN-2480 only modestly inhibits PRAK.