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Melanocortin receptor 4
A melanocortin receptor 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P32245]
Synonyms
MC4-R
Research
Bioassay Publications (53)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 3 (5.66) | 18.2507 |
| 2000's | 25 (47.17) | 29.6817 |
| 2010's | 20 (37.74) | 24.3611 |
| 2020's | 5 (9.43) | 2.80 |
Compounds (19)
Drugs with Inhibition Measurements
Drugs with Activation Measurements
CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists.Journal of medicinal chemistry, , 03-10, Volume: 65, Issue:5, 2022
Late-Stage Functionalization with Cysteine Staples Generates Potent and Selective Melanocortin Receptor-1 Agonists.Journal of medicinal chemistry, , 10-13, Volume: 65, Issue:19, 2022
Structure-Based Design of Melanocortin 4 Receptor Ligands Based on the SHU-9119-hMC4R Cocrystal Structure†.Journal of medicinal chemistry, , 01-14, Volume: 64, Issue:1, 2021
Melanocortin 1 Receptor Agonists Based on a Bivalent, Bicyclic Peptide Framework.Journal of medicinal chemistry, , 07-22, Volume: 64, Issue:14, 2021
Development of Macrocyclic Peptidomimetics Containing Constrained α,α-Dialkylated Amino Acids with Potent and Selective Activity at Human Melanocortin Receptors.Journal of medicinal chemistry, , 05-10, Volume: 61, Issue:9, 2018
Development of Novel Melanocortin Receptor Agonists Based on the Cyclic Peptide Framework of Sunflower Trypsin Inhibitor-1.Journal of medicinal chemistry, , 04-26, Volume: 61, Issue:8, 2018
Replacement of Arg with Nle and modified D-Phe in the core sequence of MSHs, Ac-His-D-Phe-Arg-Trp-NHEuropean journal of medicinal chemistry, , May-10, Volume: 151, 2018
Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists.Journal of medicinal chemistry, , 11-09, Volume: 60, Issue:21, 2017
Discovery of Novel Potent and Selective Agonists at the Melanocortin-3 Receptor.Journal of medicinal chemistry, , Dec-24, Volume: 58, Issue:24, 2015
Azepinone-Containing Tetrapeptide Analogues of Melanotropin Lead to Selective hMC4R Agonists and hMC5R Antagonist.ACS medicinal chemistry letters, , Feb-12, Volume: 6, Issue:2, 2015
Cyclic lactam hybrid α-MSH/Agouti-related protein (AGRP) analogues with nanomolar range binding affinities at the human melanocortin receptors.Bioorganic & medicinal chemistry letters, , May-15, Volume: 21, Issue:10, 2011
Substitution of arginine with proline and proline derivatives in melanocyte-stimulating hormones leads to selectivity for human melanocortin 4 receptor.Journal of medicinal chemistry, , Jun-25, Volume: 52, Issue:12, 2009
Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor.Journal of medicinal chemistry, , Jan-24, Volume: 51, Issue:2, 2008
Design, synthesis, and biological evaluation of new cyclic melanotropin peptide analogues selective for the human melanocortin-4 receptor.Journal of medicinal chemistry, , Nov-16, Volume: 49, Issue:23, 2006
Development of cyclic gamma-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities.Journal of medicinal chemistry, , Mar-23, Volume: 49, Issue:6, 2006
Design, synthesis, and biological evaluation of a new class of small molecule peptide mimetics targeting the melanocortin receptors.Bioorganic & medicinal chemistry letters, , Oct-15, Volume: 16, Issue:20, 2006
Peptide science: exploring the use of chemical principles and interdisciplinary collaboration for understanding life processes.Journal of medicinal chemistry, , Sep-25, Volume: 46, Issue:20, 2003
Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.Bioorganic & medicinal chemistry letters, , Apr-07, Volume: 13, Issue:7, 2003
Biological and conformational examination of stereochemical modifications using the template melanotropin peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on human melanocortin receptors.Journal of medicinal chemistry, , May-23, Volume: 40, Issue:11, 1997
Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.Bioorganic & medicinal chemistry, , May-15, Volume: 16, Issue:10, 2008
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.Journal of medicinal chemistry, , Feb-09, Volume: 49, Issue:3, 2006
A potent and selective nonpeptide antagonist of the melanocortin-4 receptor induces food intake in satiated mice.Bioorganic & medicinal chemistry letters, , May-16, Volume: 15, Issue:10, 2005
Late-Stage Functionalization with Cysteine Staples Generates Potent and Selective Melanocortin Receptor-1 Agonists.Journal of medicinal chemistry, , 10-13, Volume: 65, Issue:19, 2022
Melanocortin 1 Receptor Agonists Based on a Bivalent, Bicyclic Peptide Framework.Journal of medicinal chemistry, , 07-22, Volume: 64, Issue:14, 2021
Development of Novel Melanocortin Receptor Agonists Based on the Cyclic Peptide Framework of Sunflower Trypsin Inhibitor-1.Journal of medicinal chemistry, , 04-26, Volume: 61, Issue:8, 2018
Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective α-melanocyte-stimulating hormone (α-MSH) analogues.Journal of medicinal chemistry, , Mar-08, Volume: 55, Issue:5, 2012
Design, synthesis, and evaluation of proline and pyrrolidine based melanocortin receptor agonists. A conformationally restricted dipeptide mimic approach.Journal of medicinal chemistry, , Jul-27, Volume: 49, Issue:15, 2006
Sub-nanomolar hMC1R agonists by end-capping of the melanocortin tetrapeptide His-D-Phe-Arg-Trp-NH(2).Bioorganic & medicinal chemistry letters, , Aug-18, Volume: 13, Issue:16, 2003
Developing a Biased Unmatched Bivalent Ligand (BUmBL) Design Strategy to Target the GPCR Homodimer Allosteric Signaling (cAMP over β-Arrestin 2 Recruitment) Within the Melanocortin Receptors.Journal of medicinal chemistry, , 01-10, Volume: 62, Issue:1, 2019
Replacement of Arg with Nle and modified D-Phe in the core sequence of MSHs, Ac-His-D-Phe-Arg-Trp-NHEuropean journal of medicinal chemistry, , May-10, Volume: 151, 2018
Identification of tetrapeptides from a mixture based positional scanning library that can restore nM full agonist function of the L106P, I69T, I102S, A219V, C271Y, and C271R human melanocortin-4 polymorphic receptors (hMC4Rs).Journal of medicinal chemistry, , Jun-12, Volume: 57, Issue:11, 2014
Design, synthesis, and biological studies of efficient multivalent melanotropin ligands: tools toward melanoma diagnosis and treatment.Journal of medicinal chemistry, , Oct-27, Volume: 54, Issue:20, 2011
Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC1R and MC4R.Journal of medicinal chemistry, , Jul-04, Volume: 40, Issue:14, 1997
Late-Stage Functionalization with Cysteine Staples Generates Potent and Selective Melanocortin Receptor-1 Agonists.Journal of medicinal chemistry, , 10-13, Volume: 65, Issue:19, 2022
Melanocortin 1 Receptor Agonists Based on a Bivalent, Bicyclic Peptide Framework.Journal of medicinal chemistry, , 07-22, Volume: 64, Issue:14, 2021
Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists.Journal of medicinal chemistry, , 11-09, Volume: 60, Issue:21, 2017
Identification of tetrapeptides from a mixture based positional scanning library that can restore nM full agonist function of the L106P, I69T, I102S, A219V, C271Y, and C271R human melanocortin-4 polymorphic receptors (hMC4Rs).Journal of medicinal chemistry, , Jun-12, Volume: 57, Issue:11, 2014
Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective α-melanocyte-stimulating hormone (α-MSH) analogues.Journal of medicinal chemistry, , Mar-08, Volume: 55, Issue:5, 2012
Discovery of a selective small-molecule melanocortin-4 receptor agonist with efficacy in a pilot study of sexual dysfunction in humans.Journal of medicinal chemistry, , Apr-22, Volume: 53, Issue:8, 2010
Design of cyclic peptides with agonist activity at melanocortin receptor-4.Bioorganic & medicinal chemistry letters, , Jul-15, Volume: 16, Issue:14, 2006
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.Journal of medicinal chemistry, , Feb-09, Volume: 49, Issue:3, 2006
2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists.Bioorganic & medicinal chemistry letters, , Apr-15, Volume: 15, Issue:8, 2005
Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtBioorganic & medicinal chemistry letters, , Aug-01, Volume: 15, Issue:15, 2005
Novel 3D pharmacophore of alpha-MSH/gamma-MSH hybrids leads to selective human MC1R and MC3R analogues.Journal of medicinal chemistry, , Mar-24, Volume: 48, Issue:6, 2005
Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist.Bioorganic & medicinal chemistry letters, , Jan-03, Volume: 15, Issue:1, 2005
Aryl piperazine melanocortin MC4 receptor agonists.Bioorganic & medicinal chemistry letters, , Nov-03, Volume: 13, Issue:21, 2003
Peptide science: exploring the use of chemical principles and interdisciplinary collaboration for understanding life processes.Journal of medicinal chemistry, , Sep-25, Volume: 46, Issue:20, 2003
Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: histidine substitution.Bioorganic & medicinal chemistry letters, , Jan-06, Volume: 13, Issue:1, 2003
Structure-activity relationships of novel cyclic alpha-MSH/beta-MSH hybrid analogues that lead to potent and selective ligands for the human MC3R and human MC5R.Journal of medicinal chemistry, , Aug-14, Volume: 46, Issue:17, 2003
Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.Bioorganic & medicinal chemistry letters, , Sep-02, Volume: 12, Issue:17, 2002
Biological and conformational examination of stereochemical modifications using the template melanotropin peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on human melanocortin receptors.Journal of medicinal chemistry, , May-23, Volume: 40, Issue:11, 1997
Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors.Journal of medicinal chemistry, , Sep-01, Volume: 38, Issue:18, 1995
Incorporation of Agouti-Related Protein (AgRP) Human Single Nucleotide Polymorphisms (SNPs) in the AgRP-Derived Macrocyclic Scaffold c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] Decreases Melanocortin-4 Receptor Antagonist Potency and Results in the Discovery of MJournal of medicinal chemistry, , 03-12, Volume: 63, Issue:5, 2020
Human β-Defensin 1 and β-Defensin 3 (Mouse Ortholog mBD14) Function as Full Endogenous Agonists at Select Melanocortin Receptors.Journal of medicinal chemistry, , 04-26, Volume: 61, Issue:8, 2018
Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CHBioorganic & medicinal chemistry, , 01-15, Volume: 25, Issue:2, 2017
Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists.Journal of medicinal chemistry, , 11-09, Volume: 60, Issue:21, 2017
Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents.Bioorganic & medicinal chemistry, , Apr-15, Volume: 24, Issue:8, 2016
Identification of tetrapeptides from a mixture based positional scanning library that can restore nM full agonist function of the L106P, I69T, I102S, A219V, C271Y, and C271R human melanocortin-4 polymorphic receptors (hMC4Rs).Journal of medicinal chemistry, , Jun-12, Volume: 57, Issue:11, 2014
Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor.Bioorganic & medicinal chemistry, , May-15, Volume: 21, Issue:10, 2013
Synthesis and structure-activity relationship studies in serotonin 5-HT(1A) receptor agonists based on fused pyrrolidone scaffolds.European journal of medicinal chemistry, , Volume: 63, 2013
Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective α-melanocyte-stimulating hormone (α-MSH) analogues.Journal of medicinal chemistry, , Mar-08, Volume: 55, Issue:5, 2012
Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.Journal of medicinal chemistry, , Dec-08, Volume: 54, Issue:23, 2011
cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.Journal of medicinal chemistry, , Nov-27, Volume: 51, Issue:22, 2008
Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor activation.Journal of medicinal chemistry, , Feb-09, Volume: 49, Issue:3, 2006
Novel 3D pharmacophore of alpha-MSH/gamma-MSH hybrids leads to selective human MC1R and MC3R analogues.Journal of medicinal chemistry, , Mar-24, Volume: 48, Issue:6, 2005
Peptide science: exploring the use of chemical principles and interdisciplinary collaboration for understanding life processes.Journal of medicinal chemistry, , Sep-25, Volume: 46, Issue:20, 2003
Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: histidine substitution.Bioorganic & medicinal chemistry letters, , Jan-06, Volume: 13, Issue:1, 2003
Sub-nanomolar hMC1R agonists by end-capping of the melanocortin tetrapeptide His-D-Phe-Arg-Trp-NH(2).Bioorganic & medicinal chemistry letters, , Aug-18, Volume: 13, Issue:16, 2003
Structure-activity relationships of novel cyclic alpha-MSH/beta-MSH hybrid analogues that lead to potent and selective ligands for the human MC3R and human MC5R.Journal of medicinal chemistry, , Aug-14, Volume: 46, Issue:17, 2003
Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.Bioorganic & medicinal chemistry letters, , Sep-02, Volume: 12, Issue:17, 2002
D-Amino acid scan of gamma-melanocyte-stimulating hormone: importance of Trp(8) on human MC3 receptor selectivity.Journal of medicinal chemistry, , Dec-28, Volume: 43, Issue:26, 2000
Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC1R and MC4R.Journal of medicinal chemistry, , Jul-04, Volume: 40, Issue:14, 1997
Biological and conformational examination of stereochemical modifications using the template melanotropin peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on human melanocortin receptors.Journal of medicinal chemistry, , May-23, Volume: 40, Issue:11, 1997
Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors.Journal of medicinal chemistry, , Sep-01, Volume: 38, Issue:18, 1995
Enables
This protein enables 6 target(s):
| Target | Category | Definition |
|---|
| melanocortin receptor activity | molecular function | Combining with melanocortin to initiate a change in cell activity. [GOC:ai] |
| melanocyte-stimulating hormone receptor activity | molecular function | Combining with melanocyte-stimulating hormone to initiate a change in cell activity. [GOC:jl, PMID:7581459] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| peptide hormone binding | molecular function | Binding to a peptide with hormonal activity in animals. [GOC:jl, ISBN:0198506732] |
| ubiquitin protein ligase binding | molecular function | Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins. [GOC:vp] |
| neuropeptide binding | molecular function | Interacting selectively and non-covalently and stoichiometrically with neuropeptides, peptides with direct synaptic effects (peptide neurotransmitters) or indirect modulatory effects on the nervous system (peptide neuromodulators). [http://www.wormbook.org/chapters/www_neuropeptides/neuropeptides.html] |
Located In
This protein is located in 2 target(s):
| Target | Category | Definition |
|---|
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| membrane | cellular component | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. [GOC:dos, GOC:mah, ISBN:0815316194] |
Active In
This protein is active in 2 target(s):
| Target | Category | Definition |
|---|
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
Involved In
This protein is involved in 13 target(s):
| Target | Category | Definition |
|---|
| diet induced thermogenesis | biological process | The process that results in increased metabolic rate in tissues of an organism. It is triggered by the detection of dietary excess. This process is achieved via signaling in the sympathetic nervous system. [PMID:12161655] |
| energy reserve metabolic process | biological process | The chemical reactions and pathways by which a cell derives energy from stored compounds such as fats or glycogen. [GOC:mah] |
| adenylate cyclase-modulating G protein-coupled receptor signaling pathway | biological process | A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation or inhibition of adenylyl cyclase activity and a subsequent change in the intracellular concentration of cyclic AMP (cAMP). [GOC:mah, GOC:signaling, ISBN:0815316194] |
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | biological process | A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation of adenylyl cyclase activity which results in an increase in the intracellular concentration of cyclic AMP (cAMP). This pathway is negatively regulated by phosphodiesterase, which cleaves cAMP and terminates the signaling. [GOC:dph, GOC:mah, GOC:signaling, GOC:tb, ISBN:0815316194] |
| feeding behavior | biological process | Behavior associated with the intake of food. [GOC:mah] |
| insulin secretion | biological process | The regulated release of proinsulin from secretory granules accompanied by cleavage of proinsulin to form mature insulin. In vertebrates, insulin is secreted from B granules in the B cells of the vertebrate pancreas and from insulin-producing cells in insects. [GOC:mah, ISBN:0198506732] |
| response to insulin | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. [GOC:mah, ISBN:0198506732] |
| positive regulation of bone resorption | biological process | Any process that activates or increases the frequency, rate or extent of bone resorption. [GOC:go_curators] |
| regulation of eating behavior | biological process | Any process that modulates the frequency, rate or extent of eating behavior. [GO_REF:0000058, GOC:TermGenie, PMID:11961051] |
| response to melanocyte-stimulating hormone | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a melanocyte-stimulating hormone stimulus. The binding of any one of three melanocyte-stimulating hormones causes dispersal of melanosomes in melanophores of poikilothermic vertebrates. [PMID:17036007] |
| negative regulation of feeding behavior | biological process | Any process that stops, prevents or reduces the frequency, rate or extent of feeding behavior. [GOC:obol] |
| regulation of grooming behavior | biological process | Any process that modulates the frequency, rate or extent of grooming behavior. [GOC:BHF] |
| regulation of metabolic process | biological process | Any process that modulates the frequency, rate or extent of the chemical reactions and pathways within a cell or an organism. [GOC:go_curators] |