AZ12861903
Preclinical pharmacology
AZ12861903 is a high affinity inverse agonist of GHS-R1a with binding IC50 values of 6.7nM and 39nM against human and mouse receptors respectively. AZ12861903 has good oral exposure and CNS exposure has been measured in rodent (free brain:plasma = 0.42 and 1.3 in mouse and rat respectively).
Treatment with AZ12861903 in vivo reduced acute (6 h) food intake in free feeding mice in line with free target coverage in brain. This effect was demonstrated to be mediated by GHS-R1a since null (KO) mice showed no significant feed intake reduction when dosed with AZ12861903.
Suitable for and exclusions
AZ12861903 is suitable for preclinical experiments only and, at this time, there is no clinically enabled molecule available for translation to clinical studies.
Mechanism of Action
Growth hormone secretagogue receptor type 1a (GHS-R1a) inverse agonist; ghrelin receptor inverse agonist
Original Therapeutic Area
Cardiovascular, Renal and Metabolism
CNS Penetrant
Yes
Route of administration
Oral
Modality
Small Molecule
Additional Information
1. McCoull W., et al. (2014).
Journal of Medicinal Chemistry 2014, 57, 14, 6128–6140 DOI: 10.1021/jm500610n.