Mechanism of action: Melanin concentrating hormone receptor 1 (MCH1) antagonist and acetylcholinesterase (AChE) inhibitor
AZD3857 is a potent dual MCH1 receptor antagonist (Ki 8.4nM) and reversible acetylcholinesterase (AChE) inhibitor (IC50 51nM). Potency in mice and rats corresponds well to potency at the human MCH1 receptor and retains potency for AChE. AZD3857 showed no efflux as measured in Caco2 cells and occupies MCH1 receptors in the mouse brain in vivo with an unbound IC50 of 1.2nM.
The compound is well tolerated and reduces body weight by reduction of body fat in Dietary Induced Obese (DIO) mice over 21 days. In acute experiments in rats, miosis was observed.
Suitable for and exclusions
Preclinical studies (proposals) only which investigate the dual biology of this molecule.