NPY Y₄ receptor Antagonist

(S)-VU0637120 is a Y4R antagonist that effectively reduces the binding response of its endogenous ligand, pancreatic polypeptide (PP), on Y4R, with an IC₅₀ value of 2.7 μM. (S)-VU0637120 binds to the allosteric site of Y4R, which is located in the core region of the Y4R transmembrane structure, near the binding pocket of pancreatic polypeptide (PP), with a K_B value of 300-400 nM. (S)-VU0637120 holds potential for research in the field of metabolic diseases.

GR231118, an analogue of the C-terminus of neuropeptide Y, is a potent , competitive and relative seletive antagonist at human neuropeptide Y Y receptor with a pK_i of 10.4. GR231118 a potent agonist at the human neuropeptide Y Y4 receptor (pEC₅₀=8.6; pK_i=9.6) and a weak agonist at the human and rat neuropeptide YY2 and Y5 receptors. GR231118 also has high affinity for the mouse neuropeptide Y Y6 receptor (pK_i= 8.8).

J-115814 is a potent and selective neuropeptide Y1 antagonist with K_i values of 1.4, 1.8, 1.9, >10000, 620, 6000, >10000 nM for hY1, rY1, mY1, hY2, hY4, hY5, mY6, respectively. J-115814 inhibits feeding behaviors.