TAK-632 Inhibitor CAS No. 1228591-30-7

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Chemical Characteristic

Product Name	TAK-632
CAS No.	1228591-30-7
Molecular Weight	554.51
Formula	C₂₇H₁₈F₄N₄O₃S
Chemical Name	N-[7-cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-yl]cyclopropanecarboxamide
Smiles	C1(CC1)C(=O)Nc1sc2c(n1)ccc(c2C#N)Oc1cc(c(cc1)F)NC(=O)Cc1cc(ccc1)C(F)(F)F
Chemical Structure

Biological activities

TAK-632 is a potent pan-RAF inhibitor.^[1,2] In vitro, TAK-632 exerts inhibition activity on pan-RAF with an IC50 of 2.4 nM. TAK-632 is a slow off-rate inhibitor of both BRAF and CRAF, and demonstrated potent inhibitory activity even at high ATP concentration against BRAF(V600E) and CRAF with IC50s of 3.3 and 5.0 nM in a biochemical assay,respectively. In vivo, in both A375 (BRAFV600E) and HMVII (NRASQ61K) xenograft models in rats, TAK-632 demonstrates regressive antitumor efficacy.^[1]Administration of TAK-632 at doses of 4??5 mg/kg in a melanoma A375 (BRAFV600E) xenograft model in rats potently inhibits the MAPK cascade in tumor cells. Furthermore, administration of TAK-632 (4??5 mg/kg) demonstrates regressive antitumor efficacy without body weight changes. Moreover, TAK-632 induces regression in HMVII (NRASQ61K) tumors and restores body weight loss derived from HMVII tumor-induced cachexia.^[2]

Protocols

In vitro, AS-604850 is dissolved in DMSO.^[1]

References

[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. Journal of medicinal chemistry, 2013, 56(16): 6478-6494.. [2] Maurer G, et al.Raf kinases in cancer - roles and therapeutic opportunities.Oncogene 2011, 30 (32), 3477-3488

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