NPY Y4 receptor
NPY Y4 receptor is a rhodopsin-like GPCR in the neuropeptide Y family, and it functions with pancreatic polypeptide (PP) in appetite regulation and energy homeostasis[1]. Mechanistically, PP-Y4R signaling links postprandial pancreatic peptide release to satiety signals that help limit excessive food intake[1]. In experimental systems, NPY4R is present in somatostatin-containing cells of pancreatic islets, duodenum, hippocampus, and hypothalamus, and PP agonism decreases somatostatin secretion from human islets[2]. Disease relevance centers on metabolic research, because NPY4R copy number correlated with BMI and waist circumference in women, while no statistically significant correlation appeared in men[3]. Compared with Y1R, Y2R, and Y5R, Y4R is distinct because it is the only subtype with high affinity to PP over NPY[1]. For experimental applications, Y4R research uses selective peptides and small molecules, including high-affinity agonists, positive allosteric modulators, and allosteric antagonists[1][4][5][6]. - Y4R distinguishes PP signaling from broader NPY receptor biology in metabolic research[1]. - NPY4R variants and copy number support genotype-informed experimental design[3][7].
References:
- [1]. Schüß C, et al. Illuminating the neuropeptide Y4 receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective. Neuropeptides. 2024 Jun;105:102416. [Content Brief]
- [2]. Kim W, et al. Pancreatic polypeptide inhibits somatostatin secretion. FEBS Lett. 2014 Aug 25;588(17):3233-9. [Content Brief]
- [3]. Shebanits K, et al. Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference. PLoS One. 2018 Apr 5;13(4):e0194668. [Content Brief]
- [4]. Kuhn KK, et al. High Affinity Agonists of the Neuropeptide Y (NPY) Y4 Receptor Derived from the C-Terminal Pentapeptide of Human Pancreatic Polypeptide (hPP): Synthesis, Stereochemical Discrimination, and Radiolabeling. J Med Chem. 2016 Jul 14;59(13):6045-58. [Content Brief]
- [5]. Schüß C, et al. Highly Selective Y4 Receptor Antagonist Binds in an Allosteric Binding Pocket. J Med Chem. 2021 Mar 11;64(5):2801-2814. [Content Brief]
- [6]. Schüß C, et al. Structure-Activity Relationship Study of the High-Affinity Neuropeptide Y4 Receptor Positive Allosteric Modulator VU0506013. J Med Chem. 2023 Jul 13;66(13):8745-8766. [Content Brief]
- [7]. Shebanits K, et al. Functional characterization in vitro of twelve naturally occurring variants of the human pancreatic polypeptide receptor NPY4R. Neuropeptides. 2019 Aug;76:101933. [Content Brief]
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NPY Y4 receptor Related Products (10)
Related Products (10)
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[Leu31,Pro34]-Neuropeptide Y (human,rat,mouse) TFA
![[Leu31,Pro34]-Neuropeptide Y (human,rat,mouse) TFA](https://file.medchemexpress.com/product_pic/hy-p1323a.gif "Click to View [Leu31,Pro34]-Neuropeptide Y (human,rat,mouse) TFA Product Detail")
0 ImagesCat. No.: HY-P1323APurity: 98.00%[Leu31,Pro34]-Neuropeptide Y(human,rat) TFA is a specific neuropeptide Y Y1 receptor agonist. [Leu31,Pro34]-Neuropeptide Y(human,rat) TFA slao activates Y4, Y5. [Leu31,Pro34]-Neuropeptide Y(human,rat) TFA can increase blood pressure in anesthetized rats and increases food intake.
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[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide
![[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide](https://file.medchemexpress.com/product_pic/hy-p1324.gif "Click to View [cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide Product Detail")
0 Images[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide is a potent and selective neuropeptide Y Y5 receptor agonist with an IC50 of 0.24 nM for binding to the hY5 receptor. [cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide induces a high amount of food intake.
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(S)-VU0637120
0 Images(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 KB value of 300-400 nM. (S)-VU0637120 holds potential for research in the field of metabolic diseases.
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VU0506013
0 ImagesCat. No.: HY-149593CAS No.: 1207036-87-0VU0506013 is a selective positive allosteric modulator of Y4R (KB = 34.9 nM). VU0506013 can be used in the development of anti-obesity agents targeting Y4R.
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[Leu31,Pro34]-Neuropeptide Y (human,rat,mouse)
![[Leu31,Pro34]-Neuropeptide Y (human,rat,mouse)](https://file.medchemexpress.com/product_pic/hy-p1323.gif "Click to View [Leu31,Pro34]-Neuropeptide Y (human,rat,mouse) Product Detail")
0 ImagesCat. No.: HY-P1323CAS No.: 132699-73-1[Leu31,Pro34]-Neuropeptide Y(human,rat) is a specific neuropeptide Y Y1 receptor agonist. [Leu31,Pro34]-Neuropeptide Y(human,rat) slao activates Y4, Y5. [Leu31,Pro34]-Neuropeptide Y(human,rat) can increase blood pressure in anesthetized rats and increases food intake.
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Pancreatic Polypeptide, rat
0 ImagesCat. No.: HY-P1532CAS No.: 90419-12-8Synonyms: Rat pancreatic polypeptidePancreatic Polypeptide, rat (Rat pancreatic polypeptide) is a rat-derived Pancreatic Polypeptide. Pancreatic Polypeptide is a preferential agonist of NPYR4. Pancreatic Polypeptide, rat protects cells against Streptozotocin (HY-13753)-induced DNA damage. Pancreatic Polypeptide, rat inhibits glucose-stimulated insulin secretion. Pancreatic Polypeptide, rat (TFA) can be used in diabetes-related research.
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BWX 46
0 ImagesCat. No.: HY-P1325CAS No.: 172997-92-1Synonyms: ((Cys31, Nva 34)-Neuropeptide Y (27-36))2BWX 46 (((Cys31, Nva 34)-Neuropeptide Y (27-36))2) is a selective Y5 receptor agonist with an IC50 value of 0.85 nM. BWX 46 can inhibit the synthesis of cAMP in Y5 cells.
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[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic polypeptide TFA
![[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic polypeptide TFA](https://file.medchemexpress.com/product_pic/hy-p1324a.gif "Click to View [cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic polypeptide TFA Product Detail")
0 ImagesCat. No.: HY-P1324A[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide is a potent and selective neuropeptide Y Y5 receptor agonist with an IC50 of 0.24 nM for binding to the hY5 receptor. [cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide induces a high amount of food intake.
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GR231118
0 ImagesCat. No.: HY-P1321CAS No.: 158859-98-4Synonyms: 1229U91; GW1229GR231118, 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 pKi of 10.4. GR231118 a potent agonist at the human neuropeptide Y Y4 receptor (pEC50=8.6; pKi=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 (pKi= 8.8).
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J-115814
0 ImagesCat. No.: HY-122021CAS No.: 329716-61-2J-115814 is a potent and selective neuropeptide Y1 antagonist with Ki 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.
