Research Triangle Institute

Development of Neuromedin Receptor 2 Antagonists as Novel Analgesics - Abstract Chronic Pain Affects Millions of Individuals Globally, Profoundly Impacting Their Quality of Life and Imposing a Significant Burden on Healthcare Systems. While Opioids Have Been the Gold Standard for Treating Moderate to Severe Pain, Their Serious Adverse Effects, Such as Dependency and Tolerance, Limit Their Clinical Utility. Consequently, There Is a Critical Need to Explore New Therapeutic Targets for More Effective and Safer Pain Management Strategies. Neuromedin U (NMU) Is a Neuropeptide That Modulates Various Physiological Functions, Including Pain Perception, Through Its Interaction With Neuromedin U Receptor 2 (NMUR2). Emerging Evidence Suggests That NMUR2 Plays a Crucial Role in the Transmission and Modulation of Pain Signals Within the Central Nervous System, and Blocking This Receptor Could Potentially Alleviate Pain. This Proposal Aims to Establish a Comprehensive Structure-activity Relationship (SAR) for Two Chemical Series of NMUR2 Antagonists, With the Goal of Optimizing Their Potency, Selectivity, and Drug-like Properties. Upon Completion of This Project, We Aim to Provide Structure-activity Relationship Data for Compound Optimization, Early-stage Adme and Pharmacokinetic Information, Laying the Foundation for Developing NMUR2 Targeting Tool Compounds and Drug Candidates for Chronic Pain Treatment.