MLN 2480 是一种可口服的选择性Raf广谱抑制剂。

MLN2480 is an oral, selective pan-Raf kinase inhibitor in Clinicalal trials.

MLN2480 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preClinicalal 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.

In vivo, MLN2480 shows antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models.MLN-2480 (37.5 mg/kg) is well tolerated in a tumor xenograft model. The combination of MLN-2480 (12.5 mg) and TAK-733 (1 mg/kg) is effective in an SK-MEL-30 xenograft model, but monotherapy with either compound produces negligible effects.

[4]Animal Models: C57BL/6J miceFormulation: 100% PEG400Dosages: 12.5 mg/kgAdministration: oral gavage

1096708-71-2

C17H12Cl2F3N7O2S

506.29

MLN2480;BIIB-024

DMSO:93 mg/mL (183.7 mM)
Ethanol:93 mg/mL (183.7 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years