Millennium Pharmaceuticals Limited

Wei Gu

Dennis Huszar

Frank Lee

Alain Stricker-Krongrad

Alain Stricker-Kongra

Doug Levinson

Sophie Lehar

Assays for the identification of compounds useful for the modulation of body weight, metabolic rate, or feeding behavior are disclosed. Such compounds are useful for the treatment body weight disorders, e.g., obesity and cachexia. The methods involve cell-free and cell-based assays that identify compounds which alter ligand binding to and/or alter the activity of GPR10, a G protein-coupled receptor, optionally followed by an in vivo assay of the effect of the compound on feeding behavior, body weight, or metabolic rate.

GPR10 as a target for identifying weight modulating compounds

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.

Screening methods for compounds useful in the regulation of body weight

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).

The present invention relates to the discovery, identification and characterization of nucleic acids that encode a novel protein differentially expressed within the TH2 cell subpopulation (hereinafter referred to as STIF). The invention encompasses STIF nucleotides, host cell expression systems, STIF proteins, fusion proteins, polypeptides and peptides, antibodies to the STIF protein, transgenic animals that express a STIF transgene, or recombinant knock-out animals that do not express the STIF protein, and compounds that modulate STIF gene expression or STIF activity that can be used for diagnosis, drug screening, clinical trial monitoring, and/or used to treat STIF based disorders, such as proliferative disorders and T-lymphocyte-related disorders including, but not limited to, chronic inflammatory diseases and disorders, such as Crohn's disease, reactive arthritis, including Lyme disease, insulin-dependent diabetes, organ-specific autoimmunity, including multiple sclerosis, Hashimoto's thyroiditis and Grave's disease, contact dermatitis, psoriasis, graft rejection, graft versus host disease, sarcoidosis, atopic conditions, such as asthma and allergy, including allergic rhinitis, gastrointestinal allergies, including food allergies, eosinophilia, conjunctivitis, glomerular nephritis, certain pathogen susceptibilities such as helminthic (e.g., leishmaniasis) and certain viral infections, including HIV, and bacterial infections, including tuberculosis and lepromatous leprosy.

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Brookline, MA, United States of America

Wei Gu