Helen Frankenthaler Foundation

Metabolic syndrome drug

Melanocortin-4 Receptor (MC4R) Agonists for the Treatment of Obesity

Melanocortin-4 Receptor (MC4R) Agonists for the Treatment of Obesity

Perspective June 17, 2006

Authors

  • Ravi P. Nargund
  • Alison M. Strack
  • Tung M. Fong

View Author Information

Journal Information

Journal of Medicinal Chemistry

Cite this: J. Med. Chem. 2006, 49, 14

Published June 17, 2006

review-article

Copyright © 2006 American Chemical Society

ACS Publications

Copyright © 2006 American Chemical Society

Note: In lieu of an abstract, this is the article's first page.

Cited By

This article is cited by 59 publications.

NumberCitation Details
1.Bethany A. Falls, Yan Zhang. Insights into the Allosteric Mechanism of Setmelanotide (RM-493) as a Potent and First-in-Class Melanocortin-4 Receptor (MC4R) Agonist To Treat Rare Genetic Disorders of Obesity through an in Silico Approach. ACS Chemical Neuroscience 2019, 10 (3) , 1055-1065.
2.Enza Lacivita, Roberto Perrone, Lucia Margari, and Marcello Leopoldo . Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions. Journal of Medicinal Chemistry 2017, 60 (22) , 9114-9141.
3.Anamika Singh, Johannes Kast, Marvin L. S. Dirain, Huisuo Huang, and Carrie Haskell-Luevano . Synthesis and Structure–Activity Relationships of Substituted Urea Derivatives on Mouse Melanocortin Receptors. ACS Chemical Neuroscience 2016, 7 (2) , 196-205.
4.Xinrong Tian, Adrian G. Switzer, Steve A. Derose, Rajesh K. Mishra, Mark G. Solinsky, Rashid N. Mumin, Frank H. Ebetino, Lalith R. Jayasinghe, Mark E. Webster, Anny-Odile Colson, Doreen Crossdoersen, Beth B. Pinney, Julie A. Farmer, Martin E. Dowty, Cindy M. Obringer, Charles A. Cruze, Melissa L. Burklow, Paula M. Suchanek, Lily Dong, Mary Kay Dirr, Russell J. Sheldon and John A. Wos. Discovery of Orally Bioavailable 1,3,4-Trisubstituted 2-Oxopiperazine-Based Melanocortin-4 Receptor Agonists as Potential Antiobesity Agents. Journal of Medicinal Chemistry 2008, 51 (19) , 6055-6066.
5.Shi-Liang Tseng, Ming-Shiu Hung, Chun-Ping Chang, Jen-Shin Song, Chia-Liang Tai, Hua-Hao Chiu, Wan-Ping Hsieh, Yinchiu Lin, Wan-Ling Chung, Chun-Wei Kuo, Chien-Huang Wu, Cheng-Ming Chu, Yen-Shih Tung, Yu-Sheng Chao and Kak-Shan Shia. Bioisosteric Replacement of the Pyrazole 5-Aryl Moiety of N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A Novel Series of Alkynylthiophenes as Potent and Selective Cannabinoid-1 Receptor Antagonists. Journal of Medicinal Chemistry 2008, 51 (17) , 5397-5412.
6.Samuel Gary, Anuradha Roy, Steven Bloom. Carbocyclic setmelanotide analogs maintain biochemical potency at melanocortin 4 receptors. Journal of Peptide Science 2025, 31 (2)
7.Hongli Li, Yuanzhong Xu, Yanyan Jiang, Zhiying Jiang, Joshua Otiz-Guzman, Jessie C. Morrill, Jing Cai, Zhengmei Mao, Yong Xu, Benjamin R. Arenkiel, Cheng Huang, Qingchun Tong. The melanocortin action is biased toward protection from weight loss in mice. Nature Communications 2023, 14 (1)
8.Huibing Zhang, Li-Nan Chen, Dehua Yang, Chunyou Mao, Qingya Shen, Wenbo Feng, Dan-Dan Shen, Antao Dai, Shanshan Xie, Yan Zhou, Jiao Qin, Jin-Peng Sun, Daniel H. Scharf, Tingjun Hou, Tianhua Zhou, Ming-Wei Wang, Yan Zhang. Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Cell Research 2021, 31 (11) , 1163-1175.
9.Zhi Luo, Han-Mei Ye, Yan Gao, Shi-Cheng Ling, Chuan-Chuan Wei, Xiaoming Zhu. Chlorella additive increased growth performance, improved appetite and immune response of juvenile crucian carp Carassius auratus. Aquaculture Research 2018, 49 (10) , 3329-3337.
10.Spiropiperidines. 2018, 194-236.
11.A. O. Shpakov, K. V. Derkach. The Melanocortin Signal System of the Hypothalamus and Its Functional State in Type 2 Diabetes Mellitus and Metabolic Syndrome. Neuroscience and Behavioral Physiology 2017, 47 (5) , 495-507.
12.Juan A. Orellana, Waldo Cerpa, Maria F. Carvajal, José M. Lerma-Cabrera, Eduardo Karahanian, Cesar Osorio-Fuentealba, Rodrigo A. Quintanilla. New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis. Frontiers in Cellular Neuroscience 2017, 11
13.Jürgen Sandow. Effects on Different Peptide Hormones. 2016, 3691-3745.
14.Sun Hongmao. Homology Modeling and Ligand-Based Molecule Design. 2016, 109-160.
15.V Margaret Jackson, Danna M Breen, Jean-Philippe Fortin, Alice Liou, J Brent Kuzmiski, A Katrina Loomis, Marie-Laure Rives, Bhavik Shah, Philip A Carpino. Latest approaches for the treatment of obesity. Expert Opinion on Drug Discovery 2015, 10 (8) , 825-839.
16.Esther CY Lee, Philip A Carpino. Melanocortin-4 Receptor Modulators for the Treatment of Obesity: a Patent Analysis (2008–2014). Pharmaceutical Patent Analyst 2015, 4 (2) , 95-107.
17.Jürgen Sandow. Effects on Different Peptide Hormones. 2015, 1-64.
18.Philipp Ermert, Kerstin Moehle, Daniel Obrecht. Macrocyclic Inhibitors of GPCR's, Integrins and Protein–Protein Interactions. 2014, 283-338.
19.Sander Kooijman, Mariëtte R. Boon, Edwin T. Parlevliet, Janine J. Geerling, Vera van de Pol, Johannes A. Romijn, Louis M. Havekes, Illiana Meurs, Patrick C.N. Rensen. Inhibition of the central melanocortin system decreases brown adipose tissue activity. Journal of Lipid Research 2014, 55 (10) , 2022-2032.
20.Miles D. Thompson, Geoffrey N. Hendy, Maire E. Percy, Daniel G. Bichet, David E. C. Cole. G Protein-Coupled Receptor Mutations and Human Genetic Disease. 2014, 153-187.
21.Alexander O. Shpakov, Kira V. Derkach. The Functional State of Hormone-Sensitive Adenylyl Cyclase Signaling System in Diabetes Mellitus. Journal of Signal Transduction 2013, 2013, 1-16.
22.Vojtěch Hainer, Irena Aldhoon Hainerová. Do we need anti‐obesity drugs?. Diabetes/Metabolism Research and Reviews 2012, 28 (s2) , 8-20.
23.Xiu-Lei Mo, Rui Yang, Ya-Xiong Tao. Functions of transmembrane domain 3 of human melanocortin-4 receptor. Journal of Molecular Endocrinology 2012, 49 (3) , 221-235.
24.J. D. Roth, L. D'Souza, P. S. Griffin, J. Athanacio, J. L. Trevaskis, R. Nazarbaghi, C. Jodka, J. Athanacio, J. Hoyt, B. Forood, D. G. Parkes. Interactions of amylinergic and melanocortinergic systems in the control of food intake and body weight in rodents. Diabetes, Obesity and Metabolism 2012, 14 (7) , 608-615.
25.Zhi-Qiang Wang, Ya-Xiong Tao. Functional studies on twenty novel naturally occurring melanocortin-4 receptor mutations. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2011, 1812 (9) , 1190-1199.
26.Qingmei Hong, Raman K. Bakshi, Brenda L. Palucki, Min K. Park, Zhixiong Ye, Shuwen He, Patrick G. Pollard, Iyassu K. Sebhat, Jian Liu, Liangqin Guo, Doreen E. Cashen, William J. Martin, David H. Weinberg, Tanya MacNeil, Rui Tang, Constantin Tamvakopoulos, Qianping Peng, Randy R. Miller, Ralph A. Stearns, Howard Y. Chen, Airu S. Chen, Alison M. Strack, Tung M. Fong, D. Euan MacIntyre, Matthew J. Wyvratt, Ravi P. Nargund. Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Bioorganic & Medicinal Chemistry Letters 2011, 21 (8) , 2330-2334.
27.References. 2011, 283-360.
28.L.I. Belen’kii, V.N. Gramenitskaya, Yu.B. Evdokimenkova. The Literature of Heterocyclic Chemistry, Part X, 2005–2007. 2011, 1-137.
29.Shuwen He, Zhixiong Ye, Peter H. Dobbelaar, Raman K. Bakshi, Qingmei Hong, James P. Dellureficio, Iyassu K. Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, Yingjie Lai, Christopher L. Franklin, Mikhail Reibarkh, Mark A. Holmes, David H. Weinberg, Tanya MacNeil, Rui Tang, Constantin Tamvakopoulos, Qianping Peng, Randy R. Miller, Ralph A. Stearns, Howard Y. Chen, Airu S. Chen, Alison M. Strack, Tung M. Fong, Matthew J. Wyvratt, Ravi P. Nargund. Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity. Bioorganic & Medicinal Chemistry Letters 2010, 20 (22) , 6524-6532.
30.Qingmei Hong, Raman K. Bakshi, James Dellureficio, Shuwen He, Zhixiong Ye, Peter H. Dobbelaar, Iyassu K. Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, Rui Tang, Rubana N. Kalyani, Tanya MacNeil, Aurawan Vongs, Charles I. Rosenblum, David H. Weinberg, Qingping Peng, Constantin Tamvakopoulos, Randy R. Miller, Ralph A. Stearns, Doreen Cashen, Willian J. Martin, Airu S. Chen, Joseph M. Metzger, Howard Y. Chen, Allison M. Strack, Tung M. Fong, Euan Maclntyre, Lex H.T. Van der Ploeg, Matthew J. Wyvratt, Ravi P. Nargund. Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands. Bioorganic & Medicinal Chemistry Letters 2010, 20 (15) , 4483-4486.
31.Shuwen He, Zhixiong Ye, Peter H. Dobbelaar, Iyassu K. Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, Yingjie Lai, Christopher L. Franklin, Raman K. Bakshi, James P. Dellureficio, Qingmei Hong, David H. Weinberg, Tanya MacNeil, Rui Tang, Alison M. Strack, Constantin Tamvakopoulos, Qianping Peng, Randy R. Miller, Ralph A. Stearns, Howard Y. Chen, Airu S. Chen, Tung M. Fong, Matthew J. Wyvratt, Ravi P. Nargund. Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity. Bioorganic & Medicinal Chemistry Letters 2010, 20 (15) , 4399-4405.
32.Liangqin Guo, Zhixiong Ye, Jian Liu, Shuwen He, Raman K. Bakshi, Iyassu K. Sebhat, Peter H. Dobbelaar, Qingmei Hong, Tianying Jian, James P. Dellureficio, Nancy N. Tsou, Richard G. Ball, David H. Weinberg, Tanya MacNeil, Rui Tang, Constantin Tamvakopoulos, Qianping Peng, Howard Y. Chen, Airu S. Chen, William J. Martin, D. Euan MacIntyre, Alison M. Strack, Tung M. Fong, Matthew J. Wyvratt, Ravi P. Nargund. Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4′-piperidine] based melanocortin subtype-4 receptor agonists. Bioorganic & Medicinal Chemistry Letters 2010, 20 (16) , 4895-4900.
33.Marco De Amici, Clelia Dallanoce, Ulrike Holzgrabe, Christian Tränkle, Klaus Mohr. Allosteric ligands for G protein-coupled receptors: A novel strategy with attractive therapeutic opportunities. Medicinal Research Reviews 2010, 30 (3) , 463-549.
34.Shuwen He, Zhixiong Ye, Peter H. Dobbelaar, Iyassu K. Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, Yingjie Lai, Christopher L. Franklin, Raman K. Bakshi, James P. Dellureficio, Qingmei Hong, Nancy N. Tsou, Richard G. Ball, Doreen E. Cashen, William J. Martin, David H. Weinberg, Tanya MacNeil, Rui Tang, Constantin Tamvakopoulos, Qianping Peng, Randy R. Miller, Ralph A. Stearns, Howard Y. Chen, Airu S. Chen, Alison M. Strack, Tung M. Fong, D. Euan MacIntyre, Matthew J. Wyvratt, Ravi P. Nargund. Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist. Bioorganic & Medicinal Chemistry Letters 2010, 20 (7) , 2106-2110.