Brief Description

TAK-632 is a selective pan-RAF kinase inhibitor with IC50 values of 2.4/1.4 nM for BRAF V600E/c-RAF; > 60 fold selectivity over VEGFR.
IC50 Value: 2.4 nM (BRAF V600E); 1.4 nM (C-RAF); 160 nM (VEGFR) [1]
Target: B-Raf; C-Raf
In vitro: TAK-632 inhibited phosphorylation of MEK (pMEK) in melanoma A375 cells (BRAFV600E) with an IC50 value of 12 nM. Downstream inhibition of ERK phosphorylation (pERK) was also observed in A375 cells with an IC50 value of 16 nM [1]. TAK-632 suppresses RAF activity in BRAF wild-type cells with minimal RAF paradoxical activation. Our analysis using RNAi and TAK-632 in preclinical models reveals that the MAPK pathway of NRAS-mutated melanoma cells is highly dependent on RAF. TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer, probably because of its slow dissociation from RAF. As a result, TAK-632 demonstrates potent anti-proliferative effects both on NRAS-mutated melanoma cells and BRAF-mutated melanoma cells with acquired resistance to BRAF inhibitors through NRAS mutation or BRAF truncation. Furthermore, we demonstrate that the combination of TAK-632 and the MAPK kinase (MEK) inhibitor TAK-733 exhibits synergistic anti-proliferative effects on these cells [2].
References on TAK-632:
[1]. Okaniwa M, et al. Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. J Med Chem. 2013 Aug 22;56(16):6478-94.
[2]. Nakamura A, et al. Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor-resistant melanoma. Cancer Res. 2013 Oct 11.

Solubility

in DMSO > 10 mM

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid