TRANSGLUTAMINASE 2 INHIBITOR II ERW1041E (C15-1304-529)

General description

A cell-permeable, dihydroisoxazole compound that acts as an active-site directed, acyl-donor substrate competitive inhibitor of transglutaminase 2 (TG2, K_i = 11 µM). Shown to bind to the active site cysteine. Blocks 5-biotinylamido pentylamine (5BP)-induced TG2 activation in C57BL/6 mice lung in a dose-dependent manner and reduces hypoxia-induced pulmonary hypertension. Blocks poly(I:C)-induced TG2 activity in small intestine without affecting villous atrophy. Exhibits good selectivity over TG3 and Factor XIIIa, but has equipotent effect on TG1. It is well-tolerated by mice (~50 mg/kg) and displays moderate pharmacokinetic properties with t1/2= 12 h.

A cell-permeable, dihydroisoxazole compound that acts as an active-site directed, acyl-donor substrate competitive inhibitor of transglutaminase 2 (TG2, K_i = 11 µM). Shown to bind to the active site cysteine. Blocks 5-biotinylamido pentylamine (5BP)-induced TG2 activation in C57BL/6 mice lung in a dose-dependent manner and reduces hypoxia-induced pulmonary hypertension. Blocks poly(I:C)-induced TG2 activity in small intestine without affecting villous atrophy. Exhibits good selectivity over TG3 and Factor XIIIa, but has equipotent effect on TG1. It is well-tolerated by mice (~50 mg/kg) and displays moderate pharmacokinetic properties with t1/2= 12 h.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Biochem/physiol Actions

Primary Target
TGM2

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Other Notes

DiRaimond, T.R., et al. 2014. ACS Chem. Biol.9, 266.
Dafik, L., et al. 2012. PLoS One.7, e30642.
Watts, R.W., et al. 2006. J. Med. Chem.49, 7493.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Molecular Weight: 461.31. Empirical Formula: C₂₀H₂₁BrN₄O₄. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. potency: 11 . μ. M K_i. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: off-white. solubility: DMSO: 100 . mg/mL. storage temp.: −. 20°C. SMILES string: C1CC(N(C1)C(: O)OCC2: CC3: CC: CC: C3N: C2)C(: O)NCC4CC(: NO4)Br. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.