University of Michigan

Columbia University

University of Kentucky Research Foundation

John J Tesmer

Donald W Landry

Roger K Sunahara

James H Woods

Diwahar L Narasimhan

Joanne MacDonald

Chang-Guo Zhan

Shi-Xian Deng

Young Min Kwon

Victor C Yang

Mei-Chuan Holden Ko

Daquan Gao

Tien-Yi Lee

Remy L Brim

Alan Robert Saltiel

Milan N Stojanovic

Hollis Showalter

Xinmin Gan

Milan N Stojanovich

Joanne Macdonald

Victor Yang

Provided herein are amlexanox analogs and methods for the treatment and/or prevention of diabetes, impaired insulin signaling, obesity, or other related diseases and conditions therewith.

Amlexanox analogs

Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.

Thermostabilization of proteins

Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides.

Anti-cocaine compositions and treatment

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Ann Arbor, MI, United States of America

John J Tesmer