Novel Myxopyronin Analogs for Broad Spectrum Antibacterial Applications

Antibacterial drugs have had a substantive impact in reducing the burden of bacterial infection globally, but bacterial infections remain one of the largest causes of human disease. The widespread emergence of pathogenic bacteria resistant to antibiotics, along with the decline in discovery of new antibacterials is now a serious threat to global public health.  RNA polymerase (RNAP) is a critical molecular machine responsible for bacterial RNA synthesis, and its key structures are conserved across various bacterial species.  RNAP inhibitors such as rifamycins are proven broad-spectrum antibacterial agents and have been approved for clinical use. Rifamycins are the first-line treatment to kill non-replicating tuberculosis bacteria as well bacterial-biofilm associated infections of medical and surgical devices. But the clinical utility of rifamycins is limited due to the emergence of bacterial strains resistant to rifamycins. Scientists at Rutgers have designed a new class of compounds that interfere with bacterial gene expression, due to their strong affinities to targets within bacterial RNAP. The compounds are combinations of rifamycin and other potent microbial metabolites that act at the level of transcription initiation and selectively inhibit the activity of bacterial RNAP and thereby transcription initiation.  Further, compounds from this invention also inhibit bacterial RNAP derivatives that are resistant to currently known inhibitors. In Summary, these novel inhibitors have significant potential of being of clinical importance with several applications in research, antibacterial prophylaxis, drug discovery along and industrial applicability 

Antibiotics, Analysis of RNA Polymerase Structure and Function, Control of Bacterial Gene Expression, Antibacterial Chemistry, Antibacterial Therapy, Drug Discovery, Antituberculosis Agents, Identification of bacterial RNAP (diagnostics, environmental-monitoring, sensor applications), Biotechnology applications, antiseptics, disinfectants and advanced-materials applications.

 

Broad spectrum, Novel target and mechanism, Active against pathogens resistant to current antibacterial agents (MRSA, RRSA, etc.), Bacteriocidal, Synergizes with approved antibacterials (rifamycins), Orally available, Active against both replicating and non-replicating bacteria.

Large patent portfolio containing both issued and pending patents. Lead compounds with in vivo proof of concept have been discovered, and efficacy, toxicological, and pharmacological studies have been performed in animals.

 

  

 

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Rutgers ID: Ebright
Category(s):
Life Sciences
Contact:
John Anthes
(848) 932-4551
john.anthes@rutgers.edu
Inventors:
Richard Ebright
Keywords:
Drug Discovery
Metabolic Diseases
Supplementary Material