A cell-permeable cyclohexenecarboxylate that disrupts TLR4 interaction with adaptor molecules TIRAP and TRAM by selectively binding to TLR4, but not TLR1-3 or TLR5-10, via TLR4 intracellular Cys747 residue. Shown to effectively inhibit TLR4-mediated signaling events, including LPS-induced NO and inflammatory cytokines production in murine RAW264.7 macrophages (IC50 = 1.8, 1.3, and 1.9 nM, respectively, against NO, IL-6, and TNF-alpha production), TLR4/TIRAP-dependent NF-kappaB activity as well as TLR4/TIRAP- and TLR4/TRAM-dependent ISRE activity (IC50<300 nm) in hek293-htlr4 d2-cd14 transfected with either tirap or tram. when administered at an i.v. dose of 3 mg g, tak-242 is reported to completely prevent lps- (7 mg g, i.p.) induced death in mice in vivo. complete elimination of septic shock-induced death can be extended to live e. coli-infected mice when co-administered with ceftazidime (3 mg g tak-242 and 20 mg g ceftazidime, i.v.).<>
Synonyms: InSolution TLR4 Inhibitor, TAK-242 - CAS 243984-11-4 - Calbiochem; Ethyl-(6R)-6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate, ®-Ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-enecarboxylate, TLR4 Inhibitor, TAK-242 InSolution; TLR4 Inhibitor, TAK-242 InSolution, Ethyl-(6R)-6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate, ®-Ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-enecarboxylate
Molecular Formula: C15H17ClFNO4S
Molecular Weight: 361.82
Linear Structural Formula: C15H17ClFNO4S
Purity: >=98% (HPLC)
Biochem Physiol Actions: Reversible: no
Legal Information: CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Other Notes: Matsunaga, N., et al. 2011. Mol. Pharmacol.79, 34.Takashima, K., et al. 2009. Br. J. Pharmacol.157, 1250.Li, M., et al. 2006. Mol. Pharmacol.69, 1288.Yamada, M., et al. 2005. J. Med. Chem.48, 7457.