University of Notre Dame Du Lac

Washington University

Wayne State University

Mayland Chang

Shahriar Mobashery

Mijoon Lee

Derong Ding

Rafael Fridman

Gautam Dantas

Kevin Forsberg

Masahiro Ikejiri

Mitchell Pesesky

Renee Bouley

Patrick Gonzales

Sebastian Testero

Erika Leemans

Marc Boudreau

Peter I O'Daniel

Edward Spink

Dusan Hesek

infection (CDI) is a public health threat that results in 14,000 annual deaths in the United States. Challenges involve the production of CDI spores that can remain dormant for years and the production of toxins that damage the gut. Current therapies for CDI include vancomycin and metronidazole, but neither inhibits spore or toxin production. Thus, recurrence of infection occurs in 25% of patients and there are no antibiotics that are effective for multiple recurrences. We describe oxadiazoles with activity against, including the highly virulent NAP1/027 strain with increased production of toxins A and B, as well as the additional binary toxin. Oxadiazole 2 is poorly absorbed, thus advantageously achieving high concentrations in the gut. The compound targets peptidoglycan synthesis and inhibits vegetative cells, spores, and toxin production.

Compounds for the treatment of clostridium difficile infection

The present disclosure encompasses antibacterial compositions and methods of treating bacterial infections caused by resistant bacteria.

Compositions and methods of use of antibacterial drug combinations

Compounds for the treatment ofinfection

The invention provides a newly discovered oxadiazole class of antibiotics. The oxadiazoles impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacteria such as the bacterium, including methicillin-resistant(MRSA) and vancomycin-resistant and linezolid-resistant. For example, 5-(1H-indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. Antibiotic 75b antibiotic is bactericidal and is orally bioavailable. This class of antibiotics can be used as a therapeutic agent against infections by Gram-positive bacteria such as MRSA.

Non-beta lactam antibiotics

The invention provides compounds, compositions, and methods to improve or accelerate the healing of a wound. In various embodiments, the methods can include the topical treatment of the wound with the enzyme MMP-8, or the topical treatment of the wound with MMP-8 in combination with administration of an MMP-9 inhibitor, to accelerate the healing of the wound.

Acceleration of diabetic wound healing

A new class of antibiotics effective against methicillin-resistant(MRSA) is disclosed (Formula V). Compounds of this class can impair cell-wall biosynthesis by binding to both the allosteric and the catalytic domains of penicillin-binding protein (PBP) 2a. This class of antibiotics holds promise in reversing obsolescence of staphylococcal PBPs as important targets for antibiotics. Embodiments of the invention thus provide novel antibacterial compounds that target penicillin-binding proteins and/or other important cellular targets. Methods for inhibiting the growth and/or replication of bacteria using the compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, including drug-resistant strains of. 

Quinazolinone antibiotics

The invention provides compounds, compositions, and methods for the treatment of diseases, disorders, or conditions that are modulated by matrix metalloproteinases (MMPs). The compounds can be selective MMP inhibitors, for example, selective inhibitors of MMP-2, MMP-9, and/or MMP-14. The disease, disorder, or condition can include, for example, stroke, neurological disorders, ophthalmological disorders, or wounds, such as chronic wounds or diabetic wounds.

Selective matrix metalloproteinase inhibitors

The invention provides compounds, compositions, and methods for the treatment of diseases, disorders, or conditions that are modulated by matrix metalloproteinases (MMPs). The disease, disorder, or condition can include, for example, stroke, neurological disorders, or ophthalmological disorders. The treatment can include administering a compound or composition described herein, thereby providing a prodrug compound that metabolizes to an active MMP inhibitor in vivo. The MMP inhibition can be selective inhibition, for example, selective inhibition of MMP-2, MMP-9, and/or MMP-14. Thus, the invention provides non-mutagenic prodrug compounds of the formulas described herein that result in the inhibition of MMPs upon in vivo administration.

Gelatinase inhibitors and prodrugs

A new class of antibiotics effective against methicillin-resistant(MRSA) is disclosed. Compounds of this class can impair cell-wall biosynthesis by binding to both the allosteric and the catalytic domains of penicillin-binding protein (PBP) 2a. This class of antibiotics holds promise in reversing obsolescence of staphylococcal PBPs as important targets for antibiotics. Embodiments of the invention thus provide novel antibacterial compounds that target penicillin-binding proteins and/or other important cellular targets. Methods for inhibiting the growth and/or replication of bacteria using the compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, including drug-resistant strains of

Embodiments of the present invention provide novel antibacterials that target penicillin-binding proteins or other important cellular targets. Methods for inhibiting growth (reproduction, etc.) of bacteria using compounds described herein are also provided. Various embodiments exhibit activity against gram positive bacteria, such as certain strains ofand

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Granger, IN, United States of America

Mayland Chang