Neuromedin-U receptor 2 (NMUR2)

Neuromedin-U receptor 2 (NMUR2) is a member of the family A G protein-coupled receptors primarily expressed in the central nervous system, particularly in the hypothalamus, where it serves as the main receptor for the peptides neuromedin U and neuromedin S[4][6][8]. NMUR2 activation regulates energy intake, feeding behavior, and energy expenditure, and has been implicated in the control of body weight and metabolic functions[3][6]. Recent structural studies reveal that NMUR2 has a canonical seven-transmembrane architecture and binds neuropeptides in a defined orthosteric pocket, allowing for the design of selective agonists and antagonists[1][4]. NMUR2 is of therapeutic interest for obesity and metabolic syndrome, as its stimulation decreases food intake and visceral fat in preclinical models[3][6]. Additionally, NMUR2 plays roles in pain processing, stress, smooth muscle contractility, and possibly inflammation and cancer, though clinical validation in these contexts is less advanced[7][10]. Drug discovery efforts have focused on both peptide and small-molecule agonists, but central expression poses a challenge for targeting without CNS-associated side effects[3][6][4].

Other names

G-protein coupled receptor FM-4G-protein coupled receptor TGR-1NMU2GPR66

Agonists: Activation of NMUR2 leads to decreased cyclic AMP (cAMP), increased intracellular calcium, resulting in reduced food intake and body weight, and modulation of pain signaling[3][7]. Antagonists: Block endogenous NMU/NMS peptides from activating NMUR2, theoretically could increase food intake or alter pain processing (less evidence for antagonists in humans)[4][9].