ARN19702 is a selective, orally active, reversible, and brain-penetrant N-acylethanolamine acid amidase (NAAA) inhibitor with an IC50 of 230 nM for human NAAA. ARN19702 has pain relief effects[1][2].
ARN19702 (3-10 mg/kg; po; daily; for 7 consecutive days) reduces nociception associated with Paclitaxel-induced neuropathy without development of subacute antinociceptive tolerance in male rats[1]. In male mice, ARN19702 (0.1-30 mg/kg; po) attenuates in a dose-dependent manner the spontaneous nocifensive response elicited by intraplantar formalin injection and the hypersensitivity caused by intraplantar carrageenan injection, paw incision, or sciatic nerve ligation[1].. ARN19702 (3-10 mg/kg; po) produces remarkable protective effects against multiple sclerosis in mice[2].Pharmacokinetic properties of ARN19702 in mice 3 mg/kg,i.v 3 mg/kg, p.o. Cmax (ng/mL)1660±166613±68 Tmax (min)(5.0)30 CL (mL/min/Kg)33.2±1.649±8 t1/2 (min)73.9±3.7104±16 AUCplasma (h×ng/mL)1366.8±68.3988±157 AUCbrain (h×ng/mL)404.3±109.1181±28 F (%)-72±11
[1]. Yannick Fotio, et al. Antinociceptive Profile of ARN19702, (2-Ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone, a Novel Orally Active N-Acylethanolamine Acid Amidase Inhibitor, in Animal Models. J Pharmacol Exp Ther. 2021 Aug;378(2):70-76.
[2]. Marco Migliore Dr, et al. Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis. Angew Chem Int Ed Engl. 2016 Sep 5;55(37):11193-11197.