Small Molecule Drugs that May Treat Pain

Small molecule chemistries that can activate two important G-protein coupled receptor (GPCR) targets, NPFF and the MrG receptors, represent a potential new treatment for pain.

Genomic research has shown the existence of more than 400 pharmaceutically relevant GPCRs. Most of them have no known hormones or chemistries that activate them and thus are called "orphan” receptors. NPFF receptors are prominently expressed in the spinal cord, where they mediate the analgesic responses of the peptide NPFF. The MrG receptors are orphan GPCRs that are exclusively expressed by the neurons in the dorsal root ganglia that transmit pain signals to the central nervous system.

The discovery of small molecule chemistries that activate these targets was made by researchers at Acadia Pharmacueuticals (San Diego, CA, USA). The company is systematically screening members of the GPCR gene family in the search for novel chemistries. To data, the approach has been applied to more than 100 GPCRs, and novel chemistries have been identified for more than 60 of these targets.

"The chemistries are potent, selective and drug-like,” said Mark R. Brann, Ph.D., president and chief scientific officer of Acadia. "In the case of the MrGs, we have a range of chemistries that differentiate among the subtypes.” The company also has other pain programs. One is ACP-102, which targets a GPCR receptor, and another is an advanced preclinical program that exploits muscarinic receptors. ACP-102 is soon to enter clinical development for the treatment of neuropathic pain in cancer patients.




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