AZD3857
Preclinical pharmacology
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 does not demonstrate significant 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
We are currently supporting preclinical studies which investigate the dual biology of this molecule.
Mechanism of Action
Melanin concentrating hormone receptor 1 (MCH1) antagonist and acetylcholinesterase (AChE) inhibitor
Original Therapeutic Area
Cardiovascular, Renal and Metabolism
CNS Penetrant
Yes
Route of administration
Oral
Modality
Small Molecule