Biochem/physiol Actions

Reversible: no

Cell permeable: yes

Primary TargetTLR4

General description

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-α production), TLR4/TIRAP-dependent NF-κB activity as well as TLR4/TIRAP- and TLR4/TRAM-dependent ISRE activity (IC₅₀﹤300 nM) in HEK293-hTLR4/MD2-CD14 transfected with either TIRAP or TRAM. When administered at an i.v. dose of 3 mg/kg, TAK-242 is reported to completely prevent LPS- (7 mg/kg, 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/kg TAK-242 and 20 mg/kg ceftazidime, i.v.).

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.

Packaging

Packaged under inert gas

2 mg in Glass bottle

Physical form

A 25 mM (2 mg/221 µL) sterile-filtered solution of TLR4 Inhibitor, TAK-242 (Cat. No. 614316) in DMSO.

Reconstitution

Following initial thaw, aliquot and freeze (-70°C). Aliquots are stable for up to 1 year at -70°C.

Warning

Toxicity: Standard Handling (A)