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Screening methods for compounds useful in the regulation of body weight

a technology of body weight and screening methods, applied in the direction of receptors for hormones, melanocyte-stimulating hormones, antibody ingredients, etc., can solve the problems of elusive native ligands and functions of mc3-r, mc4-r and mc5-r, and achieve the effect of modulating weight control

Inactive Publication Date: 2008-01-10
MILLENNIUM PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

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

Method used

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  • Screening methods for compounds useful in the regulation of body weight
  • Screening methods for compounds useful in the regulation of body weight
  • Screening methods for compounds useful in the regulation of body weight

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Embodiment Construction

[0032] The invention described in the subsections below encompasses screening methods (e.g., assays) for the identification of compounds which affect weight modulation. The invention also encompasses agonists and antagonists of MC4-R, including small molecules, large molecules, and antibodies, as well as nucleotide sequences that can be used to inhibit MC4-r gene expression (e.g., antisense and ribozyme molecules), and gene or regulatory sequence replacement constructs designed to enhance MC4-r gene expression (e.g., expression constructs that place the MC4-r gene under the control of a strong promoter system). Such compounds may be used to treat body weight disorders. In particular, cellular and non-cellular assays are described that can be used to identify compounds that interact with the MC4-R, e.g., modulate the activity of the MC4-R and / or bind to the MC4-R. The cell based assays can be used to identify compounds or compositions that affect the signal-transduction activity of t...

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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 α-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 ag...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K38/17A61K38/00A61K48/00C07K14/72C12Q1/68G01N33/50G01N33/74
CPCA01K2217/05A61K49/00A61K48/00A61K2039/505C07K14/723C07K2319/00C12N2799/021C12Q1/6897G01N33/5008G01N33/502G01N33/5088G01N33/5091G01N33/74G01N2500/00A01K2217/075
Inventor LEE, FRANKHUSZAR, DENNISGU, WEI
Owner MILLENNIUM PHARMA INC
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