Northwestern University

University of California

Leland Stanford Junior University

Wisconsin Alumni Research Foundation

The University of North Carolina at Chapel Hill

Friedrich-alexander-universitat Erlangen-nürnberg

University of Modena

Università Degli Studi Di Modena E Reggio Emilia

Friedrich-alexander-universität

Brian K Shoichet

Brian K Kobilka

Aashish Manglik

Peter Gmeiner

Daniela Gisela Dengler

Laura Lee Kiessling

Bryan Leo Roth

Virginia E Kincaid

Scott Weston

Grady Scott Weston

Fabio Prati

Nir London

Henry Lin

Stephen D Miller

John Irwin

Oliv Eidam

Chiara Romagnoli

Fabrio Prati

Laurence Howard

Rachael A Powers

Emilia Caselli

Susan L McGovern

Harald Hübner

Anat Levit

Described herein, inter alia, are compositions and methods for modulating mu opioid receptor activity.

Mu opioid receptor modulators

MU opioid receptor modulators

Compounds and salts thereof which inhibit microbial growth or attenuate the virulence of pathogenic microorganisms and which inhibit UDP-galactopyranose mutase (UGM). Compounds of the invention include triazolothiadiazines, particularly 3, 6, 7-substituted-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, and 4-(1H-pyrrol-3-yl) thiazoles, particularly 4-(1,2,5-substituted-1H-pyrrol-3-yl)-2-substituted thiazoles, and salts thereof. Methods for inhibiting growth or attenuating virulence of microbial pathogens including mycobacterium, for example,andand, for example,. Methods for inhibiting eukaryotic human and animal pathogens, and fungi and nematodes in particular. Methods for treatment of infections by prokaryotic and eukaryotic pathogens employing compounds of the invention.

Inhibitors of UDP-galactopyranose mutase

Compounds and salts thereof which inhibit microbial growth or attenuate the virulence of pathogenic microorganisms and which inhibit UDP-galactopyranose mutase (UGM). Compounds of the invention include triazolothiadiazines, particularly 3,6,7-substituted-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, and 4-(1H-pyrrol-3-yl) thiazoles, particularly 4-(1,2,5-substituted-1H-pyrrol-3-yl)-2-substituted thiazoles, and salts thereof. Methods for inhibiting growth or attenuating virulence of microbial pathogens including mycobacterium, for example,andand, for example,. Methods for inhibiting eukaryotic human and animal pathogens, and fungi and nematodes in particular. Methods for treatment of infections by prokaryotic and eukaryotic pathogens employing compounds of the invention.

Disclosed herein inter alia are Boron containing compounds and methods for treating infections related to antibiotic resistant microorganisms.

&#x3b2;-lactamase inhibitors

New carboxyphenyl-glycylboronic acid transition-state analog inhibitors, representative of a class of compounds effective against class C &#x3b2;-lactamase AmpC. The new compounds improve inhibition by over two-orders of magnitude compared to analogous glycylboronic acids, with Ki values as low as 1 nM.

Nanomolar &#x3b2;-lactamase inhibitors

The present invention relates to molecules that stabilize and/or enhance CD154 activity, compositions comprising these molecules, methods for using these molecules and compositions (e.g., pharmaceutical compositions) comprising them. Specifically, the molecules can be used for enhancing immune function (e.g., enhancing Th1 cytokine expression), stimulating immune responses, and/or treating certain disorders (e.g., cancer, infectious disease, and immune compromised states). The invention also relates to kits and compositions comprising the molecules.

Compositions and methods for altering immune function

&#x3b2;-lactamases are the most widespread resistance mechanism to &#x3b2;-lactam antibiotics, such as penicillins and cephalosporins. In response to these enzymes, inhibitors have been introduced. Unfortunately, these inhibitors are also &#x3b2;-lactams, and resistance to them has developed rapidly. Consequently, the present invention provides a novel structure-based approach to inhibitors of these enzymes.

Non-covalent inhibitors of AmpC &#x3b2;-lactamase

The present invention provides methods of identifying compounds that non-specifically inhibit biological reactions. The present invention further includes kits that facilitate this identification. In addition, complications of compounds for use in high throughput drug screening that have been evaluated by the disclosed methodology are also part of the present invention. Further, the invention provides methods for identifying a false positive compound previously identified as positive in a screening assay by measuring the activity of at least one biological activity in the presence and absence of a small molecule compound capable of inhibiting aggregate formation, e.g., digitonin.

Methods of identifying non-specific inhibitors of biomolecules

The invention provides novel non-&bgr;-lactam inhibitors of &bgr;-lactamases. In particular, the invention provides such inhibitors which are boronic acids of formula (1) which is set forth in the specification. These compounds may be used with &bgr;-lactam antibiotics to treat &bgr;-lactam-antibiotic-resistant bacterial infections. These compounds are also antibacterial by themselves. Finally, the invention provides a pharmaceutical composition comprising these compounds.

Inhibitors of &bgr;-lactamases and uses therefor

The invention provides novel non-&bgr;-lactam inhibitors of &bgr;-lactamases. In particular, the invention provides such inhibitors which are boronic acids of formula (1) which is set forth in the specification. These compounds may be used with &bgr;-lactam antibiotics to treat 62 -lactam-antibiotic-resistant bacterial infections. These compounds are also antibacterial by themselves. Finally, the invention provides a pharmaceutical composition comprising these compounds.

The invention provides novel non-.beta.-lactam inhibitors of .beta.-lactamases. In particular, the invention provides such inhibitors which are boronic acids of formula (1) which is set forth in the specification. These compounds may be used with .beta.-lactam antibiotics to treat .beta.-lactam-antibiotic-resistant bacterial infections. These compounds are also antibacterial by themselves. Finally, the invention provides a pharmaceutical composition comprising these compounds.

Growing community of inventors

San Francisco, CA, United States of America

Brian K Shoichet