ARN14686

ARN14686 is an activity-based affinity probe for the detection of N-acylethanolamine acid amidase (NAAA) using click chemistry. It binds covalently to the N-terminal cysteine of catalytically active NAAA to form a thioester adduct. ARN14686 inhibits the hydrolysis of the NAAA substrate PAMCA in HEK293 cells (IC50s = 6 and 13 nM for human and rat recombinant enzymes, respectively) and is selective for NAAA over acid ceramidase (IC50 = 1,200 nM for the rat enzyme). It labels NAAA in HEK293 cells overexpressing human or rat recombinant NAAA and, when used at concentrations of 1 and 10 µM, in rat lung lysosomal fractions in vitro. It also detects NAAA in lung lysosomal fractions following intravenous administration at a dose of 10 mg/kg in rats. ARN14686 (3 mg/kg) has been used to determine that catalytically active NAAA is present in inflamed rat paw in a complete Freund's adjuvant model of inflammation.Formal Name: N-[(3S)-2-oxo-3-azetidinyl]-carbamic acid, 10-undecyn-1-yl ester. CAS Number: 1628345-10-7. Synonyms: Click Tag(TM) ARN14686. Molecular Formula: C15H24N2O3. Formula Weight: 280.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 1 mg/ml. SMILES: O=C(N[C@H]1CNC1=O)OCCCCCCCCCC#C. InChi Code: InChI=1S/C15H24N2O3/c1-2-3-4-5-6-7-8-9-10-11-20-15(19)17-13-12-16-14(13)18/h1,13H,3-12H2,(H,16,18)(H,17,19)/t13-/m0/s1. InChi Key: XEXRAYPXQNELAS-ZDUSSCGKSA-N.