TAK-632 is a selective kinase inhibitor targeting pan-RAF inhibition. TAK-632 inhibited phosphorylation of MEK (pMEK) in melanoma A375 cells (BRAFV600E) with an IC50 value of 12 nM. TAK-632 suppresses RAF activity in BRAF wild-type cells with minimal RAF paradoxical activation. TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer, probably because of its slow dissociation from RAF. TAK-632 demonstrates potent antiproliferative effects both on NRAS-mutated melanoma cells and BRAF-mutated melanoma cells with acquired resistance to BRAF inhibitors through NRAS mutation or BRAF truncation.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 100 mg/mL|
|Source||Cancer Res (2013). Figure 1. TAK-632|
|Method||Western blot analysis|
|Cell Lines||A431, CsFb, and HeLa cells|
|Incubation Time||2 h|
|Results||MEK and ERK phosphorylation was modestly induced at low TAK-632 concentrations but inhibited at higher concentrations in BRAF wild-type cells|
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