Abstract: Provided herein are melanocortin 4 receptor (MC4R) agonist peptides and methods of use thereof for the treatment and/or prevention of eating disorders (e.g., overeating), metabolic disorders (e.g., disorders resulting in positive energy imbalance), emotional/mental disorders, and/or dietary or syndromic obesity. In particular, provided herein are MC4R agonist peptides that exhibit enhanced selectivity for MC4R over other melanocortin receptors (e.g., MC1R, MC2R, MC3R, MC5R) and/or are MC3R antagonists or partial agonists. The peptides herein may exhibit enhanced in vitro potency, in vivo efficacy, pharmacokinetic properties, and/or stability compared to other known melanocortin receptor binding peptides.

Abstract: Provided herein are melanocortin 3 receptor (MC3R) agonist peptides and methods of use thereof for the treatment and/or prevention of eating disorders (e.g., anorexia nervosa, cachexia, etc.), metabolic disorders (e.g., sarcopenia), endocrine and growth disorders (e.g. delayed growth and/or delayed puberty), and/or emotional/mental disorders (e.g., depression, anxiety, OCD, PTSD, etc.). In particular, provided herein are MC3R agonist peptides that exhibit enhanced selectivity for MC3R over other melanocortin receptors (e.g., melanocortin 4 receptor (MC4R), melanocortin 1 receptor (MC1R), etc.) and/or are MC4R antagonists, and methods of use thereof. MC3R agonist peptides herein may exhibit enhanced in vitro potency, in vivo efficacy and pharmacokinetic properties compared to other know MC3R agonists.