ARN19702

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].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

IC50: 230 nM (human NAAA)[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±166 613±68 Tmax (min) (5.0) 30 CL (mL/min/Kg) 33.2±1.6 49±8 t1/2 (min) 73.9±3.7 104±16 AUCplasma (h×ng/mL) 1366.8±68.3 988±157 AUCbrain (h×ng/mL) 404.3±109.1 181±28 F (%) - 72±11 Animal Model: Sprague-Dawley rats (200-220 g) injected with Paclitaxel[1] Dosage: 3 mg/kg and 10 mg/kg Administration: Oral administration; daily; for 7 consecutive days (sub-chronic) Result: Reduced nociception associated with Paclitaxel-induced neuropathy.

[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.