Joslin Diabetes Center, Inc.

Other

Beth Israel Deaconess Medical Center, Inc.

Steven E Shoelson

James D Frantz

George S Eisenbarth

Damien J Dunnington

Allison B Goldfine

Benjamin G Neel

Luis Castano

Alana M O'Reilly

Scott Pluskey

This invention relates to methods for reducing chronic subacute inflammatory states associated with obesity and improve glycemia, thereby preventing or delaying the development of type 2 diabetes (T2D) in obese subjects, or subjects with the metabolic syndrome, using non-acetylated forms of salicylate, e.g., salsalate or trilisate.

Reducing risk of type 2 diabetes (T2D)

The invention features a method of identifying, evaluating or making a compound or agent, e.g., a candidate compound or agent, for treatment of a disorder characterized by insulin resistance. The method includes evaluating the ability of a compound or agent to bind IKK-&bgr; or modulate IKK-&bgr; activity, to thereby identify a compound or agent for the treatment of a disorder characterized by insulin resistance. The invention also features compounds for treating insulin resistance identified by such methods, and methods of treating a subject having a disorder characterized by insulin resistance by administering such agents.

Method for identifying compounds for treatment of insulin resistance

The invention features a method of identifying, evaluating or making a compound or agent, e.g., a candidate compound or agent, for treatment of a disorder characterized by insulin resistance. The method includes evaluating the ability of a compound or agent to interact with, e.g., bind, IKK-&bgr;, to thereby identify a compound or agent for the treatment of a disorder characterized by insulin resistance. The invention also features compounds for treating insulin resistance identified by such methods, and methods of treating a subject having a disorder characterized by insulin resistance by administering such agents.

The invention relates to novel mutant SH2 domain containing protein tyrosine phosphatases wherein the phosphatase is partially or constitutively active; and whose ability to regulate biological processes are different from the wildtype protein tyrosine phosphatases. The invention also relates to methods of use of the novel mutants, for example, in in vitro assays to screen for binding partners and inhibitors of protein tyrosine phosphatases and in the treatment of protein tyrosine phosphatase mediated diseases or conditions.

Activated mutants of SH2-domain-containing protein tyrosine phosphatases

Isolated nucleic acid encoding a growth factor receptor binding protein-insulin receptor isoform, protein obtainable from the nucleic acid, recombinant host cells transformed with the nucleic acid and use of the protein and nucleic acid sequence are disclosed.

Growth factor receptor-binding insulin receptor

A peptide capable of inhibiting the interaction of an SH2 domain containing protein with a second protein.

Inhibition of signal transduction molecules

A therapeutic agent that includes a purified peptide bound to a cytotoxic moiety, the peptide being specifically reactive with human insulin autoantibodies and non-reactive with human insulin cell surface receptor, is disclosed.

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Natick, MA, United States of America

Steven E Shoelson