BMS-986122_product_DataBase

Bioactivity

BMS-986122 is a selective, potent positive allosteric modulator of the mu-opioid receptor (µ-OR). BMS-986122 shows potentiation of orthosteric agonist-mediated β-arrestin recruitment, adenylyl cyclase inhibition, and G protein activation. BMS-986122 potentiates DAMGO-mediated [35S]GTPγS binding in mouse brain membranes[1][2].

Invitro

BMS-986122 increases β-arrestin recruitment stimulated by endomorphin 1 (EC50=3 μM) in U2OS-OPRM1 human osteosarcoma cells expressing μ-opioid receptors. BMS-986122 potentiates endomorphin 1-induced inhibition of forskolin-stimulated adenylyl cyclase activity in CHO cells expressing human recombinant μ-opioid receptors (EC50=8.9 μM). BMS-986122 potentiates DAMGO-mediated [35S]GTPγS binding in mouse brain membranes and appears to be, at least in part, a positive affinity modulator of the μ-opioid receptor for DAMGO binding[1].BMS-986122 enhances the ability of the endogenous opioid Methionine-enkephalin (Met-Enk) to stimulate G protein activity in mouse brain homogenates without activity on its own and to enhance G protein activation to a greater extent than β-arrestin recruitment in CHO cells expressing human mu-opioid receptors. BMS-986122 increases the potency of Met-Enk to inhibit GABA release in the periaqueductal gray, an important site for antinociception[2].BMS-986122 is selective for µ-OR and has no detectable activity at the closely related δ-OR. BMS-986122 is a silent allosteric modulator at δ-OR and κ-OR[3].

Name

BMS-986122

CAS

313669-88-4

Formula

C16H15BrClNO3S2

Molar Mass

448.78

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[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]. Kandasamy R, et al. Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects. Proc Natl Acad Sci U S A. 2021;118(16):e2000017118. [3]. Livingston KE, Alt A, Canals M, Traynor JR. Pharmacologic Evidence for a Putative Conserved Allosteric Site on Opioid Receptors. Mol Pharmacol. 2018;93(2):157-167.

PeptideDB

BMS-986122

CAS: 313669-88-4 F: C16H15BrClNO3S2 W: 448.78