Millennium Pharmaceuticals Limited

Alain Stricker-Krongrad

Michael A Patane

Susan Laurene Acton

Natalie Alysia Dales

Bing Guan

Timothy D Ocain

Michael E Solomon

Alexandra E Gould

Wei Gu

James A Brown

Vivek J Kadambi

ACE-2 inhibitors for the treatment of body weight and related disorders are disclosed. ACE-2 inhibitors include peptides and small molecules. Examples of small molecule ACE-2 inhibitors include compounds of formula (I):Z-&#x39b;&#x2003;&#x2003;(I)Wherein Z is a zinc coordinating moiety and &#x39b; is an amino-acid mimicking moiety, and pharmaceutically acceptabale salts thereof. Methods of using the inhibitors and pharmaceutical compositions containing the inhibitors to treat a body weight disorder, to decrease appetite, to increase muscle mass, to decrease body fat, to treat diabetes and to treat a state associated with altered lipid metabolism, are also described.

ACE-2 modulating compounds and methods of use thereof

The invention features assays for the identification of compounds useful for the modulation of body weight. Such compounds are useful for the treatment of obesity and cachexia. The methods of the invention involve cell-free and cell-based assays that identify compounds which bind to and/or activate or inhibit the activity of GPR10, a G protein-coupled receptor, followed by an in vivo assay of the effect of the compound on feeding behavior, body weight, or metabolic rate. The invention also features compounds which bind to and/or activate or inhibit the activity of GPR10 as well as pharmaceutical compositions comprising such compounds. In addition, the invention includes nucleic acid molecules comprising a nucleotide sequence encoding all or a portion of murine GPR10, polypeptides comprising all or a portion of murine GPR10, antibodies directed against murine GPR10, and animals harboring a murine GPR10 transgene (e.g., mice overexpressing murine GPR10).

GPR10 as a target for identifying weight modulating compounds

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Lexington, MA, United States of America

Alain Stricker-Krongrad