The Scripps Research Institute

Other

US Government As Represented by the Secretary of the Army

Julius M Rebek, Jr

Kent Pryor

Edward A Wintner

Shen Gu

Pamela J Glass

Shannon Biros

Kamal U Saikh

Thomas Carell

A synthetic molecule 4210 and a therapeutic use of a synthetic small molecule 4210 for treating viral infections, especially encephalitic alphavirus infections. The compound 4210 showed antiviral efficacy by up regulation type 1 interferon (IFN) specifically IFN-&#x3b2;. The compound 4210 was designed and synthesized by a structure-based approach targeting intracellular adaptor protein, myeloid differentiation primary response protein 88 (MyD88). Besides having an antiviral effect, the compound 4210 also demonstrated therapeutic efficacy for treating inflammatory syndrome associated with Gram positive bacterial infections such as exposure to staphylococcal enterotoxin B (SEB) induced toxic shock syndrome (TSS) in mice and can potentially be used in clinical set up for treating sepsis and septic shock. In addition, the application of molecule 4210 can treat sepsis and septic shock triggered by exposure to other biological agents such asorknown to cause tularemia and glanders, respectively. The molecule 4210 has the potential for a broad-spectrum therapeutic use.

Small molecule inhibitor of MYD88 for therapeutic treatment against alphavirus and staphylococcal enterotoxin infections and toxin exposure

Functionalized pyridazine derivatives having a low molecular weight and pharmaceutical compositions thereof are useful as alpha-helix mimetics and for treating conditions and/or disorders mediated by alpha-helix-binding receptors and proteins.

Scaffolds for &#x3b1;-helix mimicry

The present invention provides novel glycoluril derivatives for use as core molecules in combinatorial chemistry. Core molecules of the present invention can contain from one to six building blocks. Preferred building blocks are substituted amine radicals. Combinatorial libraries containing such core molecules are also provided.

Glycoluril core molecules for combinatorial libraries

Methods for forming combinatorial libraries and the libraries produced thereby are provided. According to a preferred aspect of the invention, a plurality of core molecules are reacted with a plurality of different tool molecules to form a library of molecules having non-naturally occurring molecular diversity. The libraries are useful for identifying lead compounds which modulate the functional activity of a biological molecule. Protease inhibitors that have been isolated from the libraries also are disclosed.

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La Jolla, CA, United States of America

Julius M Rebek, Jr