Publications

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…

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…

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…

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…

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…

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…

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)…

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…

Authors: Yongjun Hu, Kenneth A. Gruber, David E. Smith Abstract Background Cachexia is a debilitating, life-threatening condition whose pathology includes reduced food intake accompanied by hypermetabolism, leading to a catabolic state. The hypothalamic melanocortin system is a critical regulator of metabolic rate with effects being mediated through the melanocortin-4 receptor (MC4R). MC4R activation is also…

Authors: Xinxia Zhu, Michael F. Callahan, Kenneth A. Gruber, Marek Szumowski, and Daniel L. Marks Abstract Cachexia, a devastating wasting syndrome characterized by severe weight loss with specific losses of muscle and adipose tissue, is driven by reduced food intake, increased energy expenditure, excess catabolism, and inflammation. Cachexia is associated with poor prognosis and high…