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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: 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…