Abstract G protein-coupled receptors (GPCRs) are a major family of targets for drug development; however, only a small number of GPCRs have successfully provided drugs on the market and many remain understudied for therapeutic applications. A lack of suitable tool compounds is a major obstacle to understand physiological functions of these understudied GPCRs. Neuropeptide B/W Receptor 1 (NPBWR1) has been suggested to hold great potential for several therapeutic applications, particularly for pain treatment based on its overexpression in patients' samples and in vivo studies using endogenous neuropeptides. Due to their metabolic instability and poor membrane permeability, these native neuropeptides require central administration, making them unsuitable for therapeutics development. Till date, no small molecule agonists have been discovered yet. Recognizing the unmet need to develop more stable and druglike tool compounds to facilitate research on this promising target, we propose to develop NPBWR1 agonists using a two-pronged approach, peptidomimetic design and repurposing opioid receptor ligands.

Narrative G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and constitutes a productive source of drug targets. However, many GPCRs remain understudied with little progress in the past few decades. A lack of appropriate tool compounds has been identified as a major hurdle to understand these receptors' physiological functions, preventing them from being explored for innovative therapeutic applications. This project seeks to identify and develop stable and more druglike Neuropeptide B/W Receptor 1 agonists to facilitate research on this receptor system for a variety of pathological conditions including such as pain, obesity, diabetes, anxiety, and epilepsy.