5.30656

LTA4 Epoxide Hydrolase Inhibitor, ARM1

• Synonym(s): LTA4 Epoxide Hydrolase Inhibitor, ARM1, 4-(4-Benzylphenyl)-thiazol-2-amine, Leukotriene A4 Epoxide Hydrolase Inhibitor, LTA₄ Hydrolase Inhibitorq, LTA4H Inhibitor
• Empirical Formula (Hill Notation): C₁₆H₁₄N₂S
• CAS Number: 68729-05-5
• Molecular Weight: 266.36
• UNSPSC Code: 12352200
• PubChem Substance ID: 3768902

Properties

• Assay: ≥98% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: light beige
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C
• SMILES string: C1=CC=C(C=C1)CC2=CC=C(C=C2)C3=CSC(=N3)N

Description

General description

A cell-permeable benzylphenyl-thiazolamine compound that acts as a selective inhibitor against the epoxide hydrolase activity of leukotriene A4 hydrolase (LTA4H; K_i = 2.3 µM) and inhibits A23187- (Cat. Nos. 100105 & 100106) induced leukotriene B4 (LTB₄) synthesis in primary human polymorphonuclear neutrophil (PMN) cultures (IC₅₀ = 0.5 µM). Does not affect LTA4H aminopeptidase activity toward the cleavage of Pro-Gly-pro even at a high concentratin of 100 µM. Binds to the hydrophobic pocket that accommodates LTA₄ ω-end, which is distant from the aminopeptidase active site.

A cell-permeable benzylphenyl-thiazolamine compound that selectively inhibits against the leukotriene (LT) A₄ epoxide hydrolase activity of LTA4H by occupying the same hydrophobic tunnel (K_i = 2.3 µM) targeted by LTA₄ ω-end, displaying much reduced potency against LTA4H aminopeptidase activity (% inhibition/[ARM1] = 0/100 µM & 35/1 mM; Substrate = 800 µM Pro-Gly-Pro) coordinated by E296 and the catalytic site Zn²⁺ at the adjacent hydrophilic peptide substrate-binding cavity. Shown to inhibit A23187- (Cat. Nos. 100105 & 100106) induced LTB₄ production in primary human polymorphonuclear neutrophil (PMN) cultures (IC₅₀ = 0.5 µM; ARM1 added 10 min prior to 5 min stimulation by 2.5 µM A23187). Another LTA4H inhibitor SC 57461A (CAS 423169-68-0), in comparison, inhibits both the LTA₄-to-LTB₄ conversion as well as the chemotactic tripeptide Pro-Gly-Pro degradation activity of LTA4H.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
LTA4

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Use only fresh DMSO for reconstitution.

Other Notes

Stsiapanava, A., et al. 2014. Proc. Natl. Acad. Sci. USA111, 4227.

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable