BMS-986121 is a positive allosteric modulator (PAM) of the μ opioid receptor extracted from patent WO2014107344. BMS-986121 is built on a chemical scaffold representing a new chemotype for μ receptor PAMs[1][2][3].
BMS-986121 (1 μM~1 mM) significantly augments the β-arrestin-recruitment response produced by a low concentration of endomorphin-I (PAM-detection mode). BMS-986121 significantly increases the inhibition of forskolin-stimulated adenylyl cyclase activity produced by a ∼EC10 (30 pM) concentration of endomorphin-I in CHOμ cells. BMS-986121 (100 μM) produces leftward shifts in the potency of endomorphin-I (fourfold) and leu-enkephalin (sixfold), in inhibition of forskolin-stimulated cAMP-accumulation assays in CHO-μ cells[1].
[1]. Burford NT, et al. Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor. Proc Natl Acad Sci U S A. 2013;110(26):10830-10835.
[2]. WO2014107344
[3]. Bisignano P, et al. Ligand-Based Discovery of a New Scaffold for Allosteric Modulation of the μ-Opioid Receptor. J Chem Inf Model. 2015;55(9):1836-1843.