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Review

Melanocortin receptors: new opportunities in drug discovery

Pages 61-76 | Published online: 25 Feb 2005

Keep up to date with the latest research on this topic with citation updates for this article.

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Dai Nozawa, Shigeyuki Chaki & Atsuro Nakazato. (2008) Recent advances in the development of melanocortin-4 receptor ligands. Expert Opinion on Therapeutic Patents 18:4, pages 403-427.
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PERVIN BASARAN, NESE BASARAN, IRFAN ALTUNTAS & MEHMET NUMAN TAMER. (2004) Contemporary Approaches into Obesity: Drugs and Genes. Critical Reviews in Food Science and Nutrition 44:6, pages 419-424.
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Jason D Speake & Michael J Bishop. (2002) Recent advances in the development of melanocortin-4 receptor agonists. Expert Opinion on Therapeutic Patents 12:11, pages 1631-1638.
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Per M Andersson, Arne Boman, Elisabeth Seifert, Anna Skottner & Torbjörn Lundstedt. (2001) Ligands to the melanocortin receptors. Expert Opinion on Therapeutic Patents 11:10, pages 1583-1592.
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Articles from other publishers (39)

Ivan B. Filippenkov, Julia A. Remizova, Vasily V. Stavchansky, Alina E. Denisova, Leonid V. Gubsky, Nikolay F. Myasoedov, Svetlana A. Limborska & Lyudmila V. Dergunova. (2023) Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period. Genes 14:7, pages 1382.
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Uru Malik, Lai Yue Chan, Minying Cai, Victor J. Hruby, Quentin Kaas, Norelle L. Daly & David J. Craik. (2020) Development of novel frog‐skin peptide scaffolds with selectivity towards melanocortin receptor subtypes. Peptide Science 113:4.
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Steve M. Fernandes, Yeon Sun Lee, Robert J. Gillies & Victor J. Hruby. (2014) Synthesis and evaluation of bivalent ligands for binding to the human melanocortin-4 receptor. Bioorganic & Medicinal Chemistry 22:22, pages 6360-6365.
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Giorgio Morpurgo, Nora Babudri, Bernard Fioretti, Fabio Franciolini & Luigi Catacuzzeno. (2011) Synthetic aromatic compounds interfering with melanogenesis are responsible of the rising trend of malignant melanoma incidence. Medical Hypotheses 76:3, pages 374-377.
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Maria A. Bednarek, Tanya MacNeil, Rui Tang, Tung M. Fong, M. Angeles Cabello, Marta Maroto & Ana Teran. (2008) Cyclic analogs of α-melanocyte-stimulating hormone (αMSH) with high agonist potency and selectivity at human melanocortin receptor 1b. Peptides 29:6, pages 1010-1017.
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Jarl E. S. Wikberg & Felikss Mutulis. (2008) Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction. Nature Reviews Drug Discovery 7:4, pages 307-323.
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Iyassu K. Sebhat, Yingjie Lai, Khaled Barakat, Zhixiong Ye, Rui Tang, Rubana N. Kalyani, Aurawan Vongs, Tanya MacNeil, David H. Weinberg, M. Angeles Cabello, Marta Maroto, Ana Teran, Tung M. Fong, Lex H.T. Van der Ploeg, Arthur A. Patchett & Ravi P. Nargund. (2007) Melanocortin subtype 4 receptor agonists: Structure–activity relationships about the 4-alkyl piperidine core. Bioorganic & Medicinal Chemistry Letters 17:20, pages 5720-5723.
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Maria A. Bednarek, Tanya MacNeil, Rui Tang, Tung M. Fong, M. Angeles Cabello, Marta Maroto & Ana Teran. (2007) Potent and Selective Peptide Agonists of ?-Melanocyte Stimulating Hormone (?MSH) Action at Human Melanocortin Receptor 5; their Synthesis and Biological Evaluation in vitro. Chemical Biology & Drug Design 69:5, pages 350-355.
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Maria A. Bednarek, Tanya MacNeil, Rui Tang, Tung M. Fong, M. Angeles Cabello, Marta Maroto & Ana Teran. (2007) Potent and selective agonists of α-melanotropin (αMSH) action at human melanocortin receptor 5; linear analogs of α-melanotropin. Peptides 28:5, pages 1020-1028.
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Helgi B. Schiöth, Ruta Muceniece, Ilga Mutule & Jarl E. S. Wikberg. (2006) New Melanocortin 1 Receptor Binding Motif Based on the C-Terminal Sequence of ?-Melanocyte-Stimulating Hormone. Basic <html_ent glyph="@amp;" ascii="&"/> Clinical Pharmacology <html_ent glyph="@amp;" ascii="&"/> Toxicology 99:4, pages 287-293.
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Sergei Kopanchuk, Santa Veiksina, Felikss Mutulis, Ilze Mutule, Sviatlana Yahorava, Ilona Mandrika, Ramona Petrovska, Ago Rinken & Jarl E.S. Wikberg. (2006) Kinetic evidence for tandemly arranged ligand binding sites in melanocortin 4 receptor complexes. Neurochemistry International 49:5, pages 533-542.
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Xinrong Tian, Rajesh K. Mishra, Adrian G. Switzer, X. Eric Hu, Nick Kim, Adam W. Mazur, Frank H. Ebetino, John A. Wos, Doreen Crossdoersen, Beth B. Pinney, Julie A. Farmer & Russell J. Sheldon. (2006) Design and synthesis of potent and selective 1,3,4-trisubstituted-2-oxopiperazine based melanocortin-4 receptor agonists. Bioorganic & Medicinal Chemistry Letters 16:17, pages 4668-4673.
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Yu. A. Zolotarev, O. V. Dolotov, L. S. Inozemtseva, A. K. Dadayan, E. M. Dorokhova, L. A. Andreeva, L. Yu. Alfeeva, I. A. Grivennikov & N. F. Myasoedov. (2006) Degradation of the ACTH(4-10) analog Semax in the presence of rat basal forebrain cell cultures and plasma membranes. Amino Acids 30:4, pages 403-408.
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Tricia J. Vos, Suresh Balani, Christopher Blackburn, Ryan W. Chau, M. Diana Danca, Stacey V. Drabic, Cheryl A. Farrer, Michael A. Patane, Stephen G. Stroud, David L. Yowe & Christopher F. Claiborne. (2006) Identification and structure–activity relationships of a new series of Melanocortin-4 receptor antagonists. Bioorganic & Medicinal Chemistry Letters 16:8, pages 2302-2305.
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Raman K. Bakshi, Qingmei Hong, Rui Tang, Rubana N. Kalyani, Tanya MacNeil, David H. Weinberg, Lex H.T. Van der Ploeg, Arthur A. Patchett & Ravi P. Nargund. (2006) Optimization of a privileged structure leading to potent and selective human melanocortin subtype-4 receptor ligands. Bioorganic & Medicinal Chemistry Letters 16:5, pages 1130-1133.
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Feroze Ujjainwalla, Daniel Warner, Christine Snedden, Ricky D. Grisson, Thomas F. Walsh, Matthew J. Wyvratt, Rubana N. Kalyani, Tanya MacNeil, Rui Tang, David H. Weinberg, Lex Van der Ploeg & Mark T. Goulet. (2005) Design and syntheses of melanocortin subtype-4 receptor agonists. Part 2: Discovery of the dihydropyridazinone motif. Bioorganic & Medicinal Chemistry Letters 15:18, pages 4023-4028.
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Raman K. Bakshi, Qingmei Hong, J.T. Olson, Zhixiong Ye, Iyassue K. Sebhat, David H. Weinberg, Tanya MacNeil, Rubana N. Kalyani, Rui Tang, William J. Martin, Alison Strack, Erin McGowan, Constantin Tamvakopoulos, Randy R. Miller, Ralph A. Stearns, Wei Tang, D. Euan Maclntyre, Lex H.T. van der Ploeg, Arthur A. Patchett & Ravi P. Nargund. (2005) 1-Amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid as a Tic mimetic: Application in the synthesis of potent human melanocortin-4 receptor selective agonists. Bioorganic & Medicinal Chemistry Letters 15:14, pages 3430-3433.
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Sergei Kopanchuk, Santa Veiksina, Ramona Petrovska, Ilze Mutule, Michael Szardenings, Ago Rinken & Jarl E.S. Wikberg. (2005) Co-operative regulation of ligand binding to melanocortin receptor subtypes: Evidence for interacting binding sites. European Journal of Pharmacology 512:2-3, pages 85-95.
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Brenda L. Palucki, Min K. Park, Ravi P. Nargund, Rui Tang, Tanya MacNeil, David H. Weinberg, Aurawan Vongs, Charles I. Rosenblum, George A. Doss, Randall R. Miller, Ralph A. Stearns, Qianping Peng, Constantin Tamvakopoulos, Lex H.T. Van der Ploeg & Arthur A. Patchett. (2005) 2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists. Bioorganic & Medicinal Chemistry Letters 15:8, pages 1993-1996.
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Maris Lapinsh, Santa Veiksina, Staffan Uhlén, Ramona Petrovska, Ilze Mutule, Felikss Mutulis, Sviatlana Yahorava, Peteris Prusis & Jarl E. S. Wikberg. (2005) Proteochemometric Mapping of the Interaction of Organic Compounds with Melanocortin Receptor Subtypes. Molecular Pharmacology 67:1, pages 50-59.
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Brenda L. Palucki, Min K. Park, Ravi P. Nargund, Zhixiong Ye, Iyassu K. Sebhat, Patrick G. Pollard, Rubana N. Kalyani, Rui Tang, Tanya MacNeil, David H. Weinberg, Aurawan Vongs, Charles I. Rosenblum, George A. Doss, Randall R. Miller, Ralph A. Stearns, Qianping Peng, Constantin Tamvakopoulos, Erin McGowan, William J. Martin, Joseph M. Metzger, Cherrie A. Shepherd, Alison M. Strack, D. Euan MacIntyre, Lex H.T. Van der Ploeg & Arthur A. Patchett. (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 15:1, pages 171-175.
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Ilona Mandrika, Ramona Petrovska & Jarl Wikberg. (2005) Melanocortin receptors form constitutive homo- and heterodimers. Biochemical and Biophysical Research Communications 326:2, pages 349-354.
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Joseph Pontillo, Joseph A. Tran, Beth A. Fleck, Dragan Marinkovic, Melissa Arellano, Fabio C. Tucci, Marion Lanier, Jodie Nelson, Jessica Parker, John Saunders, Brian Murphy, Alan C. Foster & Chen Chen. (2004) Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor. Bioorganic & Medicinal Chemistry Letters 14:22, pages 5605-5609.
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Joseph Pontillo, Joseph A. Tran, Melissa Arellano, Beth A. Fleck, Rajesh Huntley, Dragan Marinkovic, Marion Lanier, Jodie Nelson, Jessica Parker, John Saunders, Fabio C. Tucci, Wanlong Jiang, Caroline W. Chen, Nicole S. White, Alan C. Foster & Chen Chen. (2004) Structure–activity relationships of piperazinebenzylamines as potent and selective agonists of the human melanocortin-4 receptor. Bioorganic & Medicinal Chemistry Letters 14:17, pages 4417-4423.
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Thomas H Marsilje, Jonathan B Roses, Emily F Calderwood, Stephen G Stroud, Nancy E Forsyth, Christopher Blackburn, David L Yowe, Wenyan Miao, Stacey V Drabic, Marie D Bohane, J Scott Daniels, Ping Li, Lijun Wu, Michael A Patane & Christopher F Claiborne. (2004) Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R). Bioorganic & Medicinal Chemistry Letters 14:14, pages 3721-3725.
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Viveka Dolby, Andreas Lundqvist, Thomas Fröberg, Elke Lüllau, Judith Shaw, Folke Tjerneld & Philippe Cronet. (2004) Effects of pH, salt and time on ligand binding properties of overexpressed melanocortin 4 receptor. Journal of Biochemical and Biophysical Methods 58:3, pages 195-205.
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Denis Richard & Dana Baraboi. (2004) Circuitries Involved in the Control of Energy Homeostasis and the Hypothalamic-Pituitary-Adrenal Axis Activity. Treatments in Endocrinology 3:5, pages 269-277.
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Réjean Ruel, Timothy F. Herpin, Lawrence Iben, Guanglin Luo, Alain Martel, Helen Mason, Gail Mattson, Brigitte Poirier, Edward H. Ruediger, Dan Shi, Carl Thibault, Guixue Yu, Ildiko Antal Zimanyi, Graham S. Poindexter & John E. Macor. (2003) β-Alanine dipeptides as MC4R agonists. Bioorganic & Medicinal Chemistry Letters 13:24, pages 4341-4344.
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Feroze Ujjainwalla, Daniel Warner, Thomas F. Walsh, Matthew J. Wyvratt, Changyou Zhou, Lihu Yang, Rubana N. Kalyani, Tanya MacNeil, Lex H.T. Van der Ploeg, Charles I. Rosenblum, Rui Tang, Aurawan Vongs, David H. Weinberg & Mark T. Goulet. (2003) Design and syntheses of melanocortin subtype-4 receptor agonists: evolution of the pyridazinone archetype. Bioorganic & Medicinal Chemistry Letters 13:24, pages 4431-4435.
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Felikss Mutulis, Sviatlana Yahorava, Ilze Mutule, Aleh Yahorau, Sergei Kopanchuk, Santa Veiksina, Ago Rinken & Jarl E. S. Wikberg. (2003) A non‐peptide radioiodinated high affinity melanocortin‐4 receptor ligand. Journal of Labelled Compounds and Radiopharmaceuticals 46:11, pages 1007-1017.
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J. E.S. WIKBERG, F. MUTULIS, I. MUTULE, S. VEIKSINA, M. LAPINSH, R. PETROVSKA & P. PRUSIS. (2003) Melanocortin Receptors: Ligands and Proteochemometrics Modeling. Annals of the New York Academy of Sciences 994:1, pages 21-26.
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Ruta Muceniece, Liga Krigere, Helga Süli-Vargha & Jarl E.S. Wikberg. (2003) Effects of α-melanotropin C-terminal tripeptide analogues on macrophage NO production. Peptides 24:5, pages 701-707.
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Kevin Pan, Malcolm K Scott, Daniel H.S Lee, Louis J Fitzpatrick, Jeffery J Crooke, Ralph A Rivero, Daniel I Rosenthal, Anil H Vaidya, Boyu Zhao & Allen B Reitz. (2003) 2,3-Diaryl-5-anilino[1,2,4]thiadiazoles as melanocortin MC4 receptor agonists and their effects on feeding behavior in rats. Bioorganic & Medicinal Chemistry 11:2, pages 185-192.
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V. Klusa, B. Jansone, S. Svirskis, J. Rumaks & R. Muceniece. 2004. Chemical Probes in Biology Science at the Interface of Chemistry, Biology and Medicine. Chemical Probes in Biology Science at the Interface of Chemistry, Biology and Medicine 255 267 .
Per M. Andersson & Torbj�rn Lundstedt. (2002) Hierarchical experimental design exemplified by QSAR evaluation of a chemical library directed towards the melanocortin 4 receptor. Journal of Chemometrics 16:8-10, pages 490-496.
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Felikss Mutulis, Ilze Mutule, Maris Lapins & Jarl E.S. Wikberg. (2002) Reductive amination products containing naphthalene and indole moieties bind to melanocortin receptors. Bioorganic & Medicinal Chemistry Letters 12:7, pages 1035-1038.
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Maria A. Bednarek, Tanya MacNeil, Rui Tang, Rubana N. Kalyani, Lex H.T. Van der Ploeg & David H. Weinberg. (2001) Potent and Selective Peptide Agonists of α-Melanotropin Action at Human Melanocortin Receptor 4: Their Synthesis and Biological Evaluation in Vitro. Biochemical and Biophysical Research Communications 286:3, pages 641-645.
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Jonas Lindblom, Baiba Opmane, Felikss Mutulis, Ilze Mutule, Ramona Petrovska, Vija Klusa, Lena Bergström & Jarl E. S. Wikberg. (2001) The MC4 receptor mediates α-MSH induced release of nucleus accumbens dopamine. Neuroreport 12:10, pages 2155-2158.
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