Novel approaches to the treatment of obesity and type 2 diabetes mellitus: bioactive leptin-related synthetic peptide analogs

• Published in: Recent patents on endocrine, metabolic & immune drug discovery Vol. 5; no. 3; p. 163
• Main Author: Grasso, Patricia
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.09.2011
• Subjects: Animals; Anti-Obesity Agents - administration & dosage; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; Diabetes Mellitus, Type 2 - drug therapy; Drug Evaluation, Preclinical - methods; Drug Therapy, Combination - methods; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Leptin - administration & dosage; Leptin - agonists; Leptin - analogs & derivatives; Leptin - antagonists & inhibitors; Leptin - therapeutic use; Obesity - drug therapy; Patents as Topic; Peptides - administration & dosage; Peptides - pharmacology; Peptides - therapeutic use
• ISSN: 1872-2148
• DOI: 10.2174/187221411797265917

Leptin, the protein product of the ob gene, is primarily an adipocyte-secreted hormone, whose functional significance is rapidly expanding. Although early research efforts were focused on defining leptin's role in reversing obesity in rodents, there is now substantial evidence indicating that its influence extends to a number of hypothalamic-pituitaryendocrine axes, including adrenal, gonadal, growth hormone, pancreatic islets, and thyroid. The pleiotropic nature of leptin has been confirmed by demonstration of a role for leptin in hematopoiesis, angiogenesis, immune function, osteogenesis, reproduction, and wound healing. Unfortunately, the results of the majority of clinical trials with recombinant human leptin indicated that its effectiveness in restoring energy balance and correcting obesity-related endocrinopathies in genetically obese rodent models extended only to the management of those rare forms of human obesity caused by mutation in the ob gene. Failure of leptin in the clinic, and withdrawal of phentermine from Europe, and fenfluramine and sibutrimine from clinical use in the United States, have stimulated new approaches in the development of anti-obesity and anti-diabetes pharmacophores. These efforts are focused on utilizing leptin-related synthetic peptides as leptin receptor antagonists or leptin-related synthetic peptide analogs or mimetics. This review summarizes patents on leptin-related peptide analogs, antagonists and mimetics.