Methods of Identifying Compounds that Modulate IL-4 Receptor-Mediated IgE Synthesis Utilizing an Adenosine Kinase

Abstract

The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize an adenosine kinase as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. application Ser. No. 10 / 197,381, filed Jul. 16, 2002, the contents of which is incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to compounds that modulate processes associated with isotype switching of B cells and IgE production, methods and kits for identifying such compounds and methods of using such compounds in a variety of contexts, such as for the treatment or prevention of diseases associated with or characterized by production and / or accumulation of IgE, including anaphylactic hypersensitivity or allergic reactions, allergic rhinitis, allergic conjunctivitis, systemic mastocytosis, hyper IgE syndrome, and IgE gammopathies, atopic disorders such as atopic dermatitis, atopic eczema and atopic asthma, and B-cell lymphoma. BACKGROUND OF THE INVENTION [0003] The immune system protects the body against invasion by foreign environmental agents such as ...

AI Technical Summary

Benefits of technology

The present invention provides compounds, called AR02E8 compounds, that can inhibit the production of immunoglobulin E (IgE) and the IL-4 receptor-mediated signaling cascade involved in B-cell isotype switching. These compounds are 8-30 amino acid residue peptides or peptide analogs, or pharmaceutically-acceptable salts thereof. The invention also provides methods for using these compounds to treat or prevent diseases associated with excessive production of IgE, such as allergic reactions and allergic rhinitis. The AR02E8 compounds bind to adenosine kinases (AKs), which are involved in the IL-4 signaling cascade. The invention also provides a method for identifying other compounds that can inhibit IL-4-induced germline ε transcription and production of IgE.

Problems solved by technology

The acquired immune response, which stems from exposure to the foreign invader, is extremely complex and involves numerous types of cells that interact with one another in myriad ways to express the full range of immune response.

For example, in the process of eliminating an invading foreign substance some tissue damage may occur, typically as a result of the accumulation of immunoglobulins with non-specific effects.

However, there are instances, such as in the case of hypersensitivity or allergic reactions, where the immune response directed against even innocuous agents such as inhaled pollen, inhaled mold spores, insect bite products, medications and even foods, is so powerful that it results in severe pathological consequences or symptoms.

Even when not lethal, such anaphylactic allergic reactions produce symptoms that interfere with the enjoyment of normal life.

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