Screening methods for compounds useful in the regulation of body weight

Abstract

The present invention relates to drug screening assays, and diagnostic and therapeutic methods for the treatment of body weight disorders, such as obesity, anorexia and cachexia, utilizing the melanocortin 4-receptor (MC4-R) as the target for intervention. The invention also relates to compounds that modulate the activity or expression of the MC4-R, and the use of such compounds in the treatment of body weight disorders.

Description

1. INTRODUCTION[0001] The present invention relates to drug screening assays, and diagnostic and therapeutic methods for the treatment of body weight disorders, such as obesity, anorexia and cachexia, involving the melanocortin 4-receptor (MC4-R). The invention also relates to compounds that modulate the activity or expression of the MC4-R, and the use of such compounds in the treatment of body weight disorders.2. BACKGROUND OF THE INVENTION[0002] Melanocortins (a variety of different peptide products resulting from post-translational processing of pro-opiomelanocortin) are known to have a broad array of physiological actions. Aside from their well known effects on adrenal cortical function (e.g., by ACTH, adrenocorticotropic hormone), and on melanocytes (e.g., by .alpha.-MSH, melanocyte stimulating hormone), melanocortins have been shown to affect behavior, learning, and memory, control of the cardiovascular system, analgesia, thermoregulation, and the release of other neurohumoral...

AI Technical Summary

Benefits of technology

[0015] The invention relates to assays designed to screen for compounds or compositions that modulate MC4-R activity, i.e., compounds or compositions that act as agonists or antagonists of MC4-R, and thereby modulate weight control. To this end, cell-based assays or non-cell based assays can be used to detect compounds that interact with, e.g., bind to, a MC4-R extracellular domain ("ECD"). The cell-based assays have the advantage in that they can be used to identify compounds that affect MC4-R biological activity (i.e., signal transduction), including the identification of compounds that do not interact with a MC4-R ECD, but act on an intracellular component of the signal transduction pathway mediated by MC4-R.

Problems solved by technology

Based upon its expression pattern in the hippocampal region of the brain, a role for the MC4-R in learning and memory was proposed (Gantz, 1993, supra) but was noted to be a "pharmacological paradox" in that the MC4-R does not respond well to compounds known to have an effect on retention of learned behaviors.

Thus, despite such efforts, the native ligands and function of MC3-R, MC4-R and MC5-R remain elusive.

Images