首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Enteropeptidase: A Gene Associated with a Starvation Human Phenotype and a Novel Target for Obesity Treatment
Authors:Sandrine Braud  Marco A Ciufolini  Itzik Harosh
Institution:1. ObeTherapy Biotechnology, Evry, France.; 2. Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada.; INSERM/UMR 1048, France,
Abstract:

Background

Obesity research focuses essentially on gene targets associated with the obese phenotype. None of these targets have yet provided a viable drug therapy. Focusing instead on genes that are involved in energy absorption and that are associated with a “human starvation phenotype”, we have identified enteropeptidase (EP), a gene associated with congenital enteropeptidase deficiency, as a novel target for obesity treatment. The advantages of this target are that the gene is expressed exclusively in the brush border of the intestine; it is peripheral and not redundant.

Methodology/Principal Findings

Potent and selective EP inhibitors were designed around a boroarginine or borolysine motif. Oral administration of these compounds to mice restricted the bioavailability of dietary energy, and in a long-term treatment it significantly diminished the rate of increase in body weight, despite ad libitum food intake. No adverse reactions of the type seen with lipase inhibitors, such as diarrhea or steatorrhea, were observed. This validates EP as a novel, druggable target for obesity treatment.

Conclusions

In vivo testing of novel boroarginine or borolysine-based EP inhibitors validates a novel approach to the treatment of obesity.
Keywords:
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号