TAK-632   Click here for help

GtoPdb Ligand ID: 10387

Synonyms: compound 8B [PMID: 23906342] | TAK632
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: TAK-632 is a pan-RAF kinase inhibitor [2]. It binds human BRAF in the DFG-out conformation. TAK-632 inhibits RIPK1/3-induced necrosome formation and necroptosis, and this action was shown to be mediated by direct ligand interaction with RIPK1 and RIPK3 (and inhibition of their kinase activities) [1,3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 132.35
Molecular weight 554.1
XLogP 4.46
No. Lipinski's rules broken 0
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Canonical SMILES N#Cc1c(ccc2c1sc(n2)NC(=O)C1CC1)Oc1ccc(c(c1)NC(=O)Cc1cccc(c1)C(F)(F)F)F
Isomeric SMILES N#Cc1c(ccc2c1sc(n2)NC(=O)C1CC1)Oc1ccc(c(c1)NC(=O)Cc1cccc(c1)C(F)(F)F)F
InChI InChI=1S/C27H18F4N4O3S/c28-19-7-6-17(12-21(19)33-23(36)11-14-2-1-3-16(10-14)27(29,30)31)38-22-9-8-20-24(18(22)13-32)39-26(34-20)35-25(37)15-4-5-15/h1-3,6-10,12,15H,4-5,11H2,(H,33,36)(H,34,35,37)
1. Chen X, Zhuang C, Ren Y, Zhang H, Qin X, Hu L, Fu J, Miao Z, Chai Y, Liu ZG et al.. (2019)
Identification of the Raf kinase inhibitor TAK-632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3.
Br J Pharmacol, 176 (12): 2095-2108. [PMID:30825190]
2. Okaniwa M, Hirose M, Arita T, Yabuki M, Nakamura A, Takagi T, Kawamoto T, Uchiyama N, Sumita A, Tsutsumi S et al.. (2013)
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, 56 (16): 6478-94. [PMID:23906342]
3. Zhang H, Xu L, Qin X, Chen X, Cong H, Hu L, Chen L, Miao Z, Zhang W, Cai Z et al.. (2019)
N-(7-Cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide (TAK-632) Analogues as Novel Necroptosis Inhibitors by Targeting Receptor-Interacting Protein Kinase 3 (RIPK3): Synthesis, Structure-Activity Relationships, and in Vivo Efficacy.
J Med Chem, 62 (14): 6665-6681. [PMID:31095385]