LEI 101 hydrochloride

LEI-101 is a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist, with a pEC50 of 8 for hCB2, and a pKi of less than 4 for hERG. LEI-101 is ~100-fold more potent in binding to CB2 receptors than to CB1 receptors[1][2].

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> Cannabinoid Receptor

LEI-101 (2, 6, and 20 mg/kg, po) shows in vivo activity in a spinal nerve ligation model of neuropathic pain in rats[1]. LEI‐101 (p.o. or i.p.) at 3 or 10 mg/kg dose-dependently prevents kidney dysfunction and/or morphological damage induced by cisplatin in mice[2]. Animal Model: Neuropathy-induced mechanical allodynia in male wistar rats[1]. Dosage: 2, 6, and 20 mg/kg. Administration: PO, single dose. Result: Induced a dose-dependent antinociceptive effect after 2 h of dosing. Animal Model: Fed male Wistar rats[1]. Dosage: 1 mg/kg iv and 5 mg/kg po (Pharmacological Analysis). Administration: IV and PO. Result: Exhibited T1/2 of 1.7 h and 0.8 h for po and iv administration. Had a low clearance and 100% oral bioavailability.

[1]. Mario van der Stelt, et al. Discovery and Optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione Derivatives as a Novel Class of Selective Cannabinoid CB2 Receptor Agonists. J Med Chem. 2011 Oct 27;54(20):7350-62.

[2]. Partha Mukhopadhyay, et al. The Novel, Orally Available and Peripherally Restricted Selective Cannabinoid CB2 Receptor Agonist LEI-101 Prevents Cisplatin-Induced Nephrotoxicity. Br J Pharmacol. 2016 Feb;173(3):446-58.