BMS-986122

• CAT Number: I003236
• CAS Number: 313669-88-4
• Molecular Formula: C16H15BrClNO3S2
• Molecular Weight: 448.78
• Purity: ≥95%
• Synonyms: 2-(3-bromo-4-methoxyphenyl)-3-(4-chlorophenyl)sulfonyl-1,3-thiazolidine
• InChI: InChI=1S/C16H15BrClNO3S2/c1-22-15-7-2-11(10-14(15)17)16-19(8-9-23-16)24(20,21)13-5-3-12(18)4-6-13/h2-7,10,16H,8-9H2,1H3
• InChIKey: PNGJPVDGZNPZHY-UHFFFAOYSA-N
• SMILES: COC1=C(C=C(C=C1)C2N(CCS2)S(=O)(=O)C3=CC=C(C=C3)Cl)Br

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].
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].

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.
 [Content Brief]

[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.
 [Content Brief]

[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.
 [Content Brief]