BMS-986187
Chemical compound
From Wikipedia, the free encyclopedia
BMS-986187 is a positive allosteric modulator (PAM) of the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR).[1][2][3][4][5][6]
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| Other names | BMS986187 |
| Drug class | Opioid receptor positive allosteric modulator |
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| Formula | C31H34O4 |
| Molar mass | 470.609 g·mol−1 |
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The drug is highly potent as a DOR PAM, with an EC50 of 30 nM.[2][6] It has been found to increase the affinity of the endogenous peptide DOR agonist leu-enkephalin for the receptor by 32-fold.[2] The drug has been found to act as a biased allosteric agonist of the DOR, activating G protein signaling (EC50 = 301 nM; Emax = 92%) but with little capacity to recruit β-arrestin (EC50 = 579 μM) (bias factor = 1787).[7][8][9] Although a PAM, BMS-986187 is able to activate the DOR even in the absence of an orthosteric agonist, and as such, has been referred to as an "ago-PAM".[2]
Subsequent to its discovery, BMS-987187 was found to act as a potent KOR PAM as well.[1][4] It is also a weak μ-opioid receptor (MOR) PAM (EC50 = 3,000 nM), but has 100-fold selectivity for potentiation of the DOR over the MOR.[2][4][6] BMS-986187 has about 20- to 30-fold higher affinity for the conserved allosteric site on the DOR and KOR relative to the corresponding site on the MOR.[1][4] It is not a PAM of the nociceptin receptor, which is less homologous to the other opioid receptors.[4]
The drug was first described by 2015 and was the first selective DOR PAM as well as the first selective KOR PAM to be discovered.[3][4][6] It was identified via high-throughput screening (HTS).[2] DOR PAMs like BMS-986187 might prove to be useful in the clinical treatment of certain gastrointestinal disorders.[10][11]