Uses
MLN2480 is a RAF inhibitor that is used for the treatment of melanoma.
Definition
ChEBI: TAK-580 is a 1,3-thiazolecarboxamide that is 2-[(1R)-1-aminoethyl]-1,3-thiazole-5-carboxylic acid in which the carboxy group undergoes formal condensation with the amino group of 5-chloro-4-(trifluoromethyl)pyridin-2-amine and in which the amino group undergoes formal condensation with the carboxy group of 6-amino-5-chloropyrimidine-4-carboxylic acid. It is a pan-RAF kinase inhibitor which is currently in clinical development for the treatment of radiographically recurrent or progressive low-grade glioma in children and young adults. It has a role as an antineoplastic agent, an apoptosis inducer and a B-Raf inhibitor. It is a chloropyridine, an organofluorine compound, a secondary carboxamide, an aminopyrimidine, a pyrimidinecarboxamide and a 1,3-thiazolecarboxamide.
Biological Activity
mln2480 is an potent pan-raf kinase inhibitor.
in vitro
mln2480 inhibits mapk pathway signaling in braf mutant and some ras mutant preclinical cancer models at concentrations that are tolerated in vivo. in vitro analysis of this drug combination of mln2480 and tak-733 in cell proliferation assays demonstrates synergistic activity [1].
in vivo
mln2480 is most potent in braf mutant melanoma models but also has single agent activity in some ras mutant models. the mln2480 and tak-733 combination inhibits the growth of a broader range of ras mutant tumor models than mln2480 single agent, including primary human tumor xenograft models of melanoma and crc [2].
References
[1] elizabeth grace carideo cunniff, julie zhang, jouhara chouitar, et al. combination treatment with the investigational raf kinase inhibitor mln2480 and the investigational mek kinase inhibitor tak-733 inhibits the growth of braf mutant and ras mutant preclinical models of melanoma and crc. mol cancer ther november 2013 12; c146
[2] drew warren rasco, anthony j. olszanski, amita patnaik, et al. mln2480, an investigational oral pan-raf kinase inhibitor, in patients (pts) with relapsed or refractory solid tumors: phase i study. j clin oncol 31, 2013 (suppl; abstr 2547)
