Novel Myxopyronin Analogs for Broad Spectrum Antibacterial Applications

Richard Ebright (Inventor)

Research output: Innovation

Abstract

<meta content="MSHTML 11.00.9600.16518" name="GENERATOR"/> <meta content="MSHTML 10.00.9200.16576" name="GENERATOR"/> <meta content="MSHTML 9.00.8112.16464" name="GENERATOR"/> <font face="Arial" size="2"> <p> <font face="Palatino Linotype" size="3"> <span style="FONT-SIZE: 12pt; FONT-FAMILY: 'Times New Roman','serif'"> 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. <span style="mso-spacerun: yes"> </span> RNA polymerase (RNAP) is a critical molecular machine responsible for bacterial RNA synthesis, and its key structures are conserved across various bacterial species. <span style="mso-spacerun: yes"> </span> 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. <span style="mso-spacerun: yes"> </span> 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 </span> </font> </p> <p style="MARGIN: 0in 0in 0pt"> <font size="3"> <font face="Palatino Linotype"> <span style="FONT-SIZE: 12pt; FONT-FAMILY: 'Times New Roman','serif'; mso-bidi-font-size: 11.0pt"> 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. </span> </font> </font> </p> <p style="MARGIN: 0in 0in 0pt"> <?xml:namespace prefix = "o" ns = "urn:schemas-microsoft-com:office:office" /> <o:p> <font face="Palatino Linotype" size="3"> </font> </o:p> </p> <p style="MARGIN: 0in 0in 0pt"> <font size="3"> <font face="Palatino Linotype"> <span style="FONT-SIZE: 12pt; FONT-FAMILY: 'Times New Roman','serif'; mso-bidi-font-size: 11.0pt"> 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. </span> </font> </font> </p> <p> <font size="3"> <font face="Palatino Linotype"> <span style="FONT-SIZE: 12pt; FONT-FAMILY: 'Times New Roman','serif'"> 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. </span> </font> </font> </p> <p> <font face="Palatino Linotype" size="3"> </font> </p> <p> <font face="Palatino Linotype" size="3"> </font> </p> <p> </p> <p> Supplementary Material </p> <p> Invention Summary <br/> <br/> Market Application <br/> <br/> Advantages <br/> <br/> Intellectual Property &amp; Development Status </p> </font>
Original languageEnglish (US)
StatePublished - Jun 2013

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Rifamycins
DNA-Directed RNA Polymerases
Bacterial RNA
Anti-Bacterial Agents
Bacterial Genes
Drug Discovery
Bacteria
Bacterial Infections
Intellectual Property
Gene Expression
Local Anti-Infective Agents
Patents
Disinfectants
Environmental Monitoring
Methicillin-Resistant Staphylococcus aureus
Biofilms
Biotechnology
Toxicology
Tuberculosis
Public Health

Keywords

  • Drug Discovery
  • Metabolic Diseases

Cite this

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title = "Novel Myxopyronin Analogs for Broad Spectrum Antibacterial Applications",
abstract = "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. <?xml:namespace prefix = {"}o{"} ns = {"}urn:schemas-microsoft-com:office:office{"} /> 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. Supplementary Material Invention Summary Market Application Advantages Intellectual Property & Development Status",
keywords = "Drug Discovery, Metabolic Diseases",
author = "Richard Ebright",
year = "2013",
month = "6",
language = "English (US)",
type = "Patent",

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TY - PAT

T1 - Novel Myxopyronin Analogs for Broad Spectrum Antibacterial Applications

AU - Ebright, Richard

PY - 2013/6

Y1 - 2013/6

N2 - 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. <?xml:namespace prefix = "o" ns = "urn:schemas-microsoft-com:office:office" /> 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. Supplementary Material Invention Summary Market Application Advantages Intellectual Property & Development Status

AB - 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. <?xml:namespace prefix = "o" ns = "urn:schemas-microsoft-com:office:office" /> 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. Supplementary Material Invention Summary Market Application Advantages Intellectual Property & Development Status

KW - Drug Discovery

KW - Metabolic Diseases

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M3 - Innovation

ER -