MC3R
The melanocortin-3 receptor (MC3R) is a G protein-coupled receptor critically involved in regulating energy homeostasis and body weight[1][2]. Mechanistically, MC3R modulates hypothalamic circuits that integrate nutritional signals, influencing food intake and energy expenditure[3]. Compared with the closely related MC4R, MC3R exhibits distinct hypothalamic localization, primarily in the ventromedial (VMH), arcuate (ARC), and medial habenular (MHb) nuclei, while MC4R is more widely distributed in additional hypothalamic regions[3]. In disease models, genetic variants in MC3R have been linked to obesity phenotypes, altered insulin sensitivity, and differences in body fat composition[2]. Functionally selective small molecule agonists have been developed, showing nanomolar potency and preferential activation of MC3R over MC4R, enabling pharmacological probing of receptor-specific roles in energy balance[1][4]. These agonists exhibit variable activity across other melanocortin receptor subtypes, highlighting the need to consider off-target effects when designing experimental applications[1][5]. MC3R antagonists, including modified peptide ligands, provide complementary tools to dissect receptor-specific mechanisms and examine sexual dimorphism in energy homeostasis[6][5]. Collectively, MC3R represents a therapeutically relevant target for studying metabolic regulation and developing interventions for obesity-related disorders.
References:
- [1]. Doering SR, et al. Discovery of Nanomolar Melanocortin-3 Receptor (MC3R)-Selective Small Molecule Pyrrolidine Bis-Cyclic Guanidine Agonist Compounds Via a High-Throughput \"Unbiased\" Screening Campaign. J Med Chem. 2021 May 13;64(9):5577-5592. [Content Brief]
- [2]. Lensing CJ, et al. Ac-Trp-DPhe(p-I)-Arg-Trp-NH2, a 250-Fold Selective Melanocortin-4 Receptor (MC4R) Antagonist over the Melanocortin-3 Receptor (MC3R), Affects Energy Homeostasis in Male and Female Mice Differently. ACS Chem Neurosci. 2016 Sep 21;7(9):1283-91. [Content Brief]
- [3]. Singh A, et al. Synthesis, biophysical, and pharmacological evaluation of the melanocortin agonist AST3-88: modifications of peptide backbone at Trp 7 position lead to a potent, selective, and stable ligand of the melanocortin 4 receptor (MC4R). ACS Chem Neurosci. 2014 Oct 15;5(10):1020-31. [Content Brief]
- [4]. Lee YS, et al. A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. J Clin Endocrinol Metab. 2002 Mar;87(3):1423-6. [Content Brief]
- [5]. Harrold JA, et al. Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. Diabetes. 1999 Feb;48(2):267-71. [Content Brief]
- [6]. Fleming KA, et al. Synergistic Multiresidue Substitutions of a Macrocyclic c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] Agouti-Related Protein (AGRP) Scaffold Yield Potent and >600-Fold MC4R versus MC3R Selective Melanocortin Receptor Antagonists. J Med Chem. 2018 Sep 13;61(17):7729-7740. [Content Brief]
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MC3R Related Products (20)
Related Products (20)
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Melanotan (MT)-II
0 ImagesMelanotan (MT)-II is a melanocortin receptor agonist. Melanotan (MT)-II activates melanocortin receptor 3 and melanocortin receptor 4, and stimulates the release of central endogenous oxytocin. Melanotan (MT)-II reverses recognition memory impairment, increased anxiety levels and reduced exploratory tendency in zebrafish exposed to short-term high-fat diet. Melanotan (MT)-II improves impaired social behavior indicators in mouse models of autism spectrum disorder. Melanotan (MT)-II induces weight loss, reduces food intake and exerts anorectic effects. Melanotan (MT)-II increases intracavernous pressure and erectile activity in brown rats. Melanotan (MT)-II can be used in studies related to memory impairment, anxiety, reduced exploratory behavior, autism spectrum disorder, obesity and erectile dysfunction.
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Bremelanotide Acetate
0 ImagesSynonyms: PT-141 AcetateBremelanotide (PT-141) Acetate is a melanocortin receptor agonist. Bremelanotide Acetate can activate MC4R and increases dopamine release. Bremelanotide Acetate induces appetitive sexual behaviors, female mounting behavior, and repetitive self-grooming. Bremelanotide Acetate can be used for the research of hypoactive sexual desire disorders.
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Nonapeptide-1 acetate salt
0 ImagesCat. No.: HY-P0097ASynonyms: Melanostatine-5 acetate saltNonapeptide-1 (Melanostatine-5) acetate salt, a peptide hormone, is a selective antagonist of MC1R (Ki: 40 nM). Nonapeptide-1 acetate salt is a competitive α-MSH antagonist that potently inhibits intracellular cAMP and melanosome dispersion induced by α-MSH in melanocytes (IC50: 2.5 nM and 11 nM, respectively). Nonapeptide-1 acetate salt inhibits melanin synthesis, and can be used in the research of skin pigmentation and regulation of steroid production in the adrenal gland, skin cancer.
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Bremelanotide
0 ImagesSynonyms: PT-141Bremelanotide (PT-141) is a melanocortin receptor agonist. Bremelanotide can activate MC4R and increases dopamine release. Bremelanotide induces appetitive sexual behaviors, female mounting behavior, and repetitive self-grooming. Bremelanotide can be used for the research of hypoactive sexual desire disorders.
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PG-901
0 ImagesPG-901 is a full, selective MC5R agonist (EC50 = 0.072 nM for hMC5R). PG-901 is also a full antagonist at the hMC3R and the hMC4R (Kb: 1.0 nM and 0.53 nM, respectively). PG-901 significantly diminishes Cytokines (IL-1α, IL-1β, IL-6). PG-901 increases glucose tolerance, reduces blood glucose, decreases retinal damage.
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Melanotan (MT)-II acetate
0 ImagesCat. No.: HY-P0267ACAS No.: 1036322-26-5Melanotan (MT)-II acetate is a melanocortin receptor agonist. Melanotan (MT)-II acetate activates melanocortin receptor 3 and melanocortin receptor 4, and stimulates the release of central endogenous oxytocin. Melanotan (MT)-II acetate reverses recognition memory impairment, increased anxiety levels and reduced exploratory tendency in zebrafish exposed to short-term high-fat diet. Melanotan (MT)-II acetate improves impaired social behavior indicators in mouse models of autism spectrum disorder. Melanotan (MT)-II acetate induces weight loss, reduces food intake and exerts anorectic effects. Melanotan (MT)-II acetate increases intracavernous pressure and erectile activity in brown rats. Melanotan (MT)-II acetate can be used in studies related to memory impairment, anxiety, reduced exploratory behavior, autism spectrum disorder, obesity and erectile dysfunction.
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Nonapeptide-1
0 ImagesSynonyms: Melanostatine-5Nonapeptide-1 (Melanostatine-5), a peptide hormone, is a selective antagonist of MC1R (Ki: 40 nM). Nonapeptide-1 is a competitive α-MSH antagonist that potently inhibits intracellular cAMP and melanosome dispersion induced by α-MSH in melanocytes (IC50: 2.5 nM and 11 nM, respectively). Nonapeptide-1 inhibits melanin synthesis, and can be used in the research of skin pigmentation and regulation of steroid production in the adrenal gland, skin cancer.
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Resomelagon
0 ImagesSynonyms: AP1189Resomelagon (AP1189) is a potent, orally active melanocortin receptor (MR) agonist about MC1 and MC3. Resomelagon induces ERK1/2 phosphorylation and Ca2+ mobilization. Resomelagon has anti-inflammatory activity. Resomelagon can be used for obesity and chronic inflammation research.
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γ-1-Melanocyte Stimulating Hormone (MSH), amide
0 ImagesCat. No.: HY-P1531CAS No.: 72629-65-3γ-1-Melanocyte Stimulating Hormone (MSH), amide is a 11-amino acid peptide. γ-1-Melanocyte Stimulating Hormone (MSH) regulates sodium (Na+) balance and blood pressure through activation of the melanocortin receptor 3 (MC3-R).
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γ1-MSH
0 Imagesγ1-MSH is a melanocortin MC3 receptor agonist, with a Ki of 34 nM for the rat MC3 receptor. γ1-MSH displays ~40-fold selectivity over MC4 (Ki=1318 nM).
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[D-Trp8]-γ-MSH
![[D-Trp8]-γ-MSH](https://file.medchemexpress.com/product_pic/hy-p1217.gif "Click to View [D-Trp8]-γ-MSH Product Detail")
0 Images[D-Trp8]-γ-MSH is a potent and selective agonist of melanocortin 3 (MC3) receptor, with IC50s of 6.7 nM, 600 nM and 340 nM for hMC3, hMC4 and hMC5, respectively in CHO cells. [D-Trp8]-γ-MSH could provide protection against multiple inflammatory disorders such as rheumatoid arthritis and colitis.
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Setmelanotide monoacetate
0 ImagesSynonyms: RM-493 monoacetate; BIM-22493 monoacetate; IRC-022493 monoacetateSetmelanotide monoacetate (RM-493 monoacetate) is a blood-brain barrier-permeable, selective MC4R agonist with a Ki value of 2.1 nM for hMC4R. Setmelanotide monoacetate activates the CaMKK2/AMPK signaling pathway. Setmelanotide monoacetate mediates body weight homeostasis, feeding regulation and energy expenditure modulation; it reduces food intake, induces weight loss, decreases obesity severity, increases daytime activity and energy expenditure, lowers levels of leptin, triglycerides, fasting insulin and diastolic blood pressure, improves insulin sensitivity, glucose tolerance and fatty liver condition, and reverses respiratory depression. Setmelanotide monoacetate is applicable to research related to obesity, hyperinsulinemia, fatty liver and respiratory depression.
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Ac-c[Cys-Glu-His-d-Phe-Arg-Trp-d-Cys]-Pro-Pro-Lys-Asp-NH2
![Ac-c[Cys-Glu-His-d-Phe-Arg-Trp-d-Cys]-Pro-Pro-Lys-Asp-NH2](https://file.medchemexpress.com/product_pic/hy-p4665.gif "Click to View Ac-c[Cys-Glu-His-d-Phe-Arg-Trp-d-Cys]-Pro-Pro-Lys-Asp-NH2 Product Detail")
0 ImagesAc-c-Pro-Pro-Lys-Asp-NH2 is a selective human melanocortin 5 receptor (hMC5R) antagonist with an IC50 of 10 nM.
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[D-Trp8]-γ-MSH TFA
![[D-Trp8]-γ-MSH TFA](https://file.medchemexpress.com/product_pic/hy-p1217a.gif "Click to View [D-Trp8]-γ-MSH TFA Product Detail")
0 ImagesCat. No.: HY-P1217A[D-Trp8]-γ-MSH TFA is a potent and selective agonist of melanocortin 3 (MC3) receptor, with IC50s of 6.7 nM, 600 nM and 340 nM for hMC3, hMC4 and hMC5, respectively in CHO cells. [D-Trp8]-γ-MSH TFA could provide protection against multiple inflammatory disorders such as rheumatoid arthritis and colitis.
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RY764
0 ImagesCat. No.: HY-111131CAS No.: 491845-95-5RY746 is a selective MC4R agonist, with an EC50 of 10 nM. RY764 effectively inhibits food intake and reduces body weight gain in diet-induced obese (DIO) rat models. RY764 can be used for the study of obesity.
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(E/Z)-Resomelagon acetate
0 ImagesCat. No.: HY-168383CAS No.: 959850-74-9Synonyms: (E/Z)-AP1189 acetate(E/Z)-Resomelagon acetate is an agonist of melanocortin receptor 1 (MC1R) and MC3R with anti-inflammatory activities. (E/Z)-Resomelagon can be utilized in inflammation research.
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