ENDO 2026: Dual MC3R/MC4R Activation Drives Weight Loss, Limits Rebound, and Preserves Lean Mass in Obese Nonhuman Primates
Oral abstract at ENDO 2026 in Chicago, IL
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Dual Activation of MC3R and MC4R Drives Weight Loss and Reduces Food Intake in Male Primates with Obesity
Authors: Jillian L. Seiler, Anna C. Impastato, Emma (Xiaoyu) Zhang, Kade J. Kelley, Thomas L. Bennett, Bradley Studnitzer, Claudia R. Prindle, Benjamin H. Rajewski, Barry A. Badeau, Xinjian Jiang, Russell Potterfield, Jordan Y. Delev, Daniel L. Marks Abstract: The melanocortin system plays a central role in regulating hunger and satiety, making it an attractive target for treating metabolic disease. However, the limited clinical success of selective melanocortin-4 receptor (MC4R) agonists has prompted investigation into whether concurrent…
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The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives
Authors: Claudia R. Prindle, Thomas L. Bennett, Benjamin H. Rajewski, Kade J. Kelley, Anna C. Impastato, Russell Potterfield, Daniel L. Marks, and Jordan Y. Delev Abstract: The melanocortin system is a genetically conserved and clinically validated target for the treatment of obesity. Hundreds of studies establish the role of the melanocortin receptors, particularly the melanocortin-4…
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Dual Activation of MC3R and MC4R Drives Weight Loss and Reduces Food Intake in Obese Primates
Authors: Jillian L. Seiler, Anna C. Impastato, Emma (Xiaoyu) Zhang, Kade J. Kelley, Thomas L. Bennett, Bradley Studnitzer, Claudia R. Prindle, Benjamin H. Rajewski, Barry A. Badeau, Xinjian Jiang, Russell Potterfield, Jordan Y. Delev, Daniel L. Marks Abstract: The melanocortin system plays a central role in regulating hunger and satiety, making it an attractive target for treating metabolic disease. However, the limited clinical success of selective melanocortin-4 receptor (MC4R) agonists prompted the investigation of whether concurrent…
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Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats
Authors: Xinxia Zhu, Russell Potterfield, Kenneth A. Gruber, Emma Zhang, Samuel D. Newton, Mason A. Norgard, Peter R. Levasseur, Peng Bai, Xu Chen, Qingyang Gu, Aaron J. Grossberg, and Daniel L. Marks Abstract: Cancer patients undergoing chemotherapy often experience anorexia and weight loss that substantially deteriorates overall health, reduces treatment tolerance and quality of life, and worsens oncologic outcomes. There are currently few effective therapeutic options…
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Safety of TCMCB07, a melanocortin-4 antagonist peptide, in dogs with naturally occurring cachexia
Authors: Sandra M. Axiak-Bechtel, Stacey B. Leach, Jessica R. Newton-Northup, Rowan J. Milner, Stacey A. Fox-Alvarez, Lana I. Fagman, Kaylee A. Young, Deborah J. Tate, Zachary M. Wright, John D. Chretin, Justin W. Allen, Sean K. Yoshimoto, Kimberly A. Selting, Brian K. Flesner, Carrie R. White, Tracy Mills, Michael Aherne, Philip J. Bergman, LeAnn Qi, Kenneth A. Gruber, Michael F. Callahan Abstract Background The melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics…
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Preliminary data from the phase I study of TCMCB07, a study to assess the safety, tolerability and pharmacokinetics of the melanocortin antagonist TCMCB07 in healthy subjects
Authors: LeAnn Kuhlmann Qi, Xinxia Zhu, Kenneth Gruber, Eric J. Roeland, Russell Potterfield, and Daniel Marks Abstract Background: Cachexia is a complex wasting syndrome characterized by anorexia, an involuntary loss of adipose tissue and lean body mass, and a paradoxical increase in energy catabolism. TCMCB07 is an optimized peptide antagonist of the melanocortin type 3 and…
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Effect of melanocortin-4 receptor antagonist TCMCB07 on chemotherapy-induced anorexia and weight loss in rats
Authors: Xinxia Zhu, Eric J. Roeland, Mason A. Norgard, Kenneth Gruber, Russell Potterfield, and Daniel Marks Abstract e15196 Background: We previously reported that peripheral administration of TCMCB07, a synthetic antagonist of the type 4 melanocortin receptor (MC4R), ameliorates cancer- and chronic kidney disease-associated cachexia in rats. In this study, we used a rat model of cisplatin…
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Development of a Therapeutic Peptide for Cachexia Suggests a Platform Approach for Drug-like Peptides
Authors: Kenneth A. Gruber*Ren-Lai JiFabio GallazziShaokai JiangSteven R. Van DorenYa-Xiong TaoJessica Newton Northup Abstract During the development of a melanocortin (MC) peptide drug to treat the condition of cachexia (a hypermetabolic state producing lean body mass wasting), we were confronted with the need for peptide transport across the blood–brain barrier (BBB): the MC-4 receptors (MC4Rs)…
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Pharmacokinetics and safety of TCMCB07, a melanocortin-4 antagonist peptide in dogs
Authors: Sandra M. Axiak-Bechtel, Stacey B. Leach, David G. Scholten, Jessica R. Newton-Northup, Brendan J. Johnson, H. E. Durham, Kenneth A. Gruber, Michael F. Callahan Abstract The melanocortin-4 receptor (MC4R) antagonistic peptide TCMCB07 was developed for the treatment of cachexia. The objectives of this study were to examine pharmacokinetics and safety of TCMCB07 administered subcutaneously…