Non-beta Lactam Antibiotics (Oxadiazoles)

Tech ID: 15-017 and 07-039

Inventors: Dr. Maryland Chang & Dr. Shahriar Mobashery

Date Added: August 22, 2019

 

Overview

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A new class of oxadiazole antibiotics exhibiting activities against the bacterium Staphylococcus aureus including MRSA.

Technology Summary

Staphylococcus aureus is a human bacterial pathogen that is a leading source of infections in healthcare and community environments. In recent years MRSA has become a serious threat, with 2011 records indicating that nearly half of deaths caused by antibiotic-resistant bacteria and fungi in the US were directly attributed to MRSA infections. Of the antibiotics approved for treatment of MRSA infection, only the oxazolidinones are orally bioavailable and resistance is known for most of these antibiotics. Therefore, the discovery of new antibiotics for treatment of MRSA infections, especially orally available ones, is essential.

University of Notre Dame researchers have discovered a new class of antibiotics, the oxadiazoles. This class of antibiotics is bactericidal and impairs the synthesis of bacterial cell-wall and exhibits activity against Gram-positive bacteria, including MRSA, vancomycin-resistant enterococcus (VRE), and linezolid-resistant S. aureus. The researchers evaluated 500 derivatives of the lead structure and found one antibiotic in particular that is highly effective in mouse models of MRSA infection. The lead has favorable pharmacokinetic properties, with a long half-life, low clearance, high volume of distribution, and is orally bioavailable.

Market Advantages 

  • New class of antibiotics for otherwise antibiotic-resistant bacteria
  • Orally bioavailable
  • Synergizes in combination with β-lactam antibiotics

Technology Readiness Status

TRL 4 - Lab Validation

Intellectual Property

US Patent 9,045,442 (Antibacterial Compounds and Methods of Using Same)

PCT  US15/513,892 (Non-Beta Lactam Anti-biotics)

Patents filed in: China, Australia, Canada, Israel, India, Japan, South Korea, Mexico, New Zealand, Singapore, South Africa, and Hong Kong

Publications

Activities Of Oxadiazole Antibacterials Against Staphylococcus Aureus And Other Gram-positive Bacteria
doi: 10.1128/AAC.00453-18

In Vitro and In Vivo Synergy of the Oxadiazole Class of Antibacterials with β-Lactams
doi: 10.4155/fmc-2017-0159
 
The Oxadiazole Antibacterials
doi: 10.1016/j.mib.2016.05.009
 
Three-dimensional Qsar Analysis And Design Of New 1,2,4-oxadiazole Antibacterials
doi: 10.1016/j.bmcl.2015.12.041
 
Exploration of the Structure-Activity Relationship of 1,2,4-Oxadiazole Antibiotics
doi: 10.1016/j.bmcl.2015.06.044
 
Structure–Activity Relationship for the Oxadiazole Class of Antibiotics
doi: 10.1021/jm501661f

Discovery of a New Class of Non-β-Lactam Inhibitors of Penicillin-binding Proteins with Gram-positive Antibacterial Activity
doi: 10.1021/ja500053x

Contact

Richard Cox

rcox4@nd.edu

574.631.5158