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Ghosh S.K.,National University of Singapore | Somanadhan B.,MerLion Pharmaceuticals | Tan K.S.-W.,National University of Singapore | Butler M.S.,National University of Singapore | And 3 more authors.
Organic Letters | Year: 2012

The absolute configuration (via degradation and Marfey's derivatization studies) and the total synthesis of a novel antimalarial lipid-peptide isolated from Streptomyces sp. (IC 50 = 0.8 μM, Plasmodium falciparum 3D7) is disclosed. To this end, versatile stereocontrolled routes to nonproteinogenic amino acids (via catalytic Mannich, Sharpless methods) and enantiomeric trans fatty acids (via Evans alkylation, Kocienski-Julia olefination) have been developed. © 2012 American Chemical Society.


Research and Markets has announced the addition of the "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026 " report to their offering. The "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026" report provides an extensive study of the current landscape and the growing pipeline of new generation antibiotics targeting drug-resistant bacteria. As indicated earlier, owing to the over-prescription of antibiotics due to improper diagnosis, lack of adherence to proper dosage regimens, their widespread availability as over-the-counter (OTC) drugs, and overuse in agriculture and poultry farming, most antibiotics have been rendered ineffective. Moreover, there currently exists an expanding lag between the pace at which drug resistant bacteria evolve and the time taken for new drugs to reach the market. As a result, antibiotic drug resistance has escalated into a global threat. There are concerns that the lack of effective drugs in this domain may soon trigger the relapse of the pre-antibiotic era, in which individuals died due to day-to-day bacterial infections. According to certain studies, currently, an estimated 700,000 deaths annually are known to occur due to anti-microbial resistance worldwide. In future, the growing threat of antibiotic resistance is anticipated to prove to be more fatal than cancer. The current scenario depicts an urgent need for new antibiotics with novel mechanisms of action, having the ability to combat antibiotic resistance. The US and EU governments have amended their action plans and conducted many conferences to raise awareness about the situation among both experts in the domain and the general public. Such initiatives are addressed to support R&D strategies of companies engaged in the development of drugs to combat antibiotic resistance. Efforts are underway to assist drug developers in their clinical trial design issues, and even the simplification of regulatory pathways to expedite the time to market for such drugs. In addition, such initiatives endorse public-private partnerships in advancing scientific and clinical efforts in this domain, aid the setting up of surveillance programs to track the widespread use of antibiotics and the development of resistance, and track the growing economic burden due to this phenomenon as well. The new generation antibiotics pipeline comprises of several molecules that target infections caused by deadly pathogens classified under ESKAPE or as urgent threats by the CDC. Several start-ups have entered the market and undertaken various initiatives to develop novel antibiotics with unique mechanisms of action. - An overview of the current state of the market with respect to the key players involved, phase of development of pipeline products (clinical and preclinical/discovery), target classes of pathogens (Gram-negative versus Gram-positive), drug classes and key disease indications. In addition, we have included an insightful representation of the developer landscape, highlighting the geographical presence of key players in the industry. - Detailed profiles of approved drugs, as well as those in phase III of clinical development, highlighting information on clinical trials, their current status of development, recent developments and associated collaborations. - Insights on novel alternative therapies that are being explored/evaluated to target antibiotic resistant pathogenic bacteria; these include teixobactin, anti-microbial peptides, antisense antibacterials, quorum sensing inhibition, nano-metal based therapies and anti-biofilm agents. - Details on the most popular therapeutic areas, namely acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP) Clostridium difficile infections (CDIs), complicated intra-abdominal infections (cIAIs), complicated urinary tract infections (cUTIs) and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). For each indication, we have provided a brief description of the disease, information on its epidemiology, available treatment plans and active comparator studies of approved drug candidates that are prescribed for the aforementioned indications. - An illustrative grid representation and a bulls-eye analysis of the pipeline molecules, based on their development stage, spectrum of activity and the key indications. - Future commercial potential of the market based on a detailed opportunity analysis, for the period between 2016 and 2026. The research, analysis and insights presented in this report include potential sales of approved antibiotics and those in late stages of development. 1. Preface 2. Executive Summary 3. Introduction 4. Antibiotic Drug Resistance: Development Pipeline and Market Landscape 5. Clinical Development Analysis and Key Comparator Studies 6. New Generation Antibiotics: Marketed Drugs 7. New Generation Antibiotics: Phase III Drugs 8. Emerging Therapies to Combat Antibiotic Resistance 9. Key Therapeutic Areas 10. Market Forecast and Opportunity Analysis 11. Conclusion 12. Interview Transcripts 13. Appendix 1: Tabulated Data 14. Appendix 2: List of Companies and Organization - AAIPharma Services - ABAC Therapeutics - ANTABIO - Abbott Laboratories - Abgentis - Absynth Biologics - Achaogen - Acino Holdings - Actavis - Actelion Pharmaceuticals - Adenium Biotech - Adimab - Aequor - AiCuris - Alaxia Pharma - Albany Molecular Research (AMRI) - Allecra Therapeutics - Allergan - Angelini - Antibio Tx - Antibiotic Adjuvant - Aphios - Appili Therapeutics - Arietis Pharma - Arpida - Arsanis - Assembly Biosciences - AstraZeneca - Austell Laboratories - Aventis Pharma - BKG Pharma - BUGWORKS - Basilea Pharmaceutica - Bayer Pharma - BioVersys - Biocidium Biopharmaceuticals - Biocon - Biosearch Italia - Biovertis - Blueberry Therapeutics - C3 Jian - Calixa Therapeutics - Cantab Anti-infectives - Cardiome Pharma - Cellceutix Corporation - Cempra - Cerexa - Clinigen Group - ContraFect - Crestone - Crystal Genomics - Cubist Pharmaceuticals - CyDex Pharmaceuticals - DSM Sinochem Pharmaceuticals - Da Volterra - Daiichi Sankyo - Debiopharm International - Deinove - Demuris - Discuva - Dong Wha Pharmaceuticals - Dong-A Pharmaceutical - Durata Therapeutics - Eli Lilly - Eligo Bioscience - EnBiotix - Entasis Therapeutics - Eurofarma Laboratórios - Evolva Holding - Evotec - Eydo Pharma - FOB Synthesis - Fedora Pharmaceuticals - Forest Laboratories - Fujisawa Pharmaceuticals - GSK - Galapagos - GangaGen - GeneWEAVE - Hikma Pharmaceuticals - IASO Pharma - iNtRON Biotechnology - Immuron - Indel Therapeutics - Institute of Metagenomics and Microbial Technologies (IMMT) - InterMune - Ionis Pharmaceuticals - Isis Pharmaceuticals - Janssen-Ortho - Japan Radio Company - Johnson & Johnson - Kyorin Pharmaceutical - LegoChem Biosciences - Ligand Pharmaceuticals - Lyndra - MGB Biopharma - Macrolide Pharmaceuticals - MarBiLeads - Matinas BioPharma - MedImmune - Meiji Seika Pharma - Melinta Therapeutics - MerLion Pharmaceuticals - Merck - MethylGene - Microbecide - MicuRx Pharmaceuticals - Mirati Therapeutics - Monash University - MorphoSys - Morphochem - Motif Bio - Mutabilis - Nabriva Therapeutics - Naicon - NanoSafe Coatings - Nanotherapeutics - Navigen Pharmaceuticals - Nemesis Bioscience - Nexgen Biosciences - Nobelex Biotech - Northeastern University - Northern Antibiotics - Nosopharm - NovaBiotics - NovaDigm Therapeutics - Novexel - NovoBiotic Pharmaceuticals - Nuprim - OJ-Bio - Optimer Biotechnology - Optimer Pharmaceuticals - Osel - PENDOPHARM - Pacific Beach BioSciences - Par Pharmaceutical - Paratek Pharmaceuticals - Patheon - Peninsula Pharmaceuticals - Peptilogics - Pfizer - Pherecydes Pharma - Phico Therapeutics - Polyphor - Procarta Biosystems - Pure Actives - R-Pharm - RQx Pharmaceuticals - RaQualia Pharma - Rebiotix - Redx Pharma - Rempex Pharmaceuticals - RexC Pharmaceuticals - Rib-X Pharmaceuticals - Roche - Rx3 Pharmaceuticals - Sanofi-Aventis - SciClone Pharmaceuticals - Sequella - Seres Therapeutics - SetLance - Shionogi - Shire - SinSa Labs - Specialised Therapeutics Australia - Spero Therapeutics - Sumitomo Dainippon Pharma (DSP) - Summit Therapeutics - Synamp Pharmaceuticals - Synthetic Biologics - TAXIS Pharmaceuticals - TaiGen Biotechnology - Takeda Pharmaceutical - Talon Pharmaceuticals - Targanta Therapeutics - TechnoPhage - Techulon - Tetraphase Pharmaceuticals - The Medicines Company - TheraBor Pharmaceuticals - Theravance Biopharma - Treat Systems - Trius Therapeutics - University of Michigan Life Sciences Institute - University of Pittsburgh - Vaxdyn - VenatoRx Pharmaceuticals - Versicor Pharmaceuticals - VibioSphen - Vicuron Pharmaceuticals - ViroPharma - Vitas Pharma - Vyome Biosciences - Wakunaga Pharmaceutical - Warner Chillcott - Wockhardt - Yamanouchi Pharmaceutical - Zavante Therapeutics For more information about this report visit http://www.researchandmarkets.com/research/gqv9bz/antibacterial


Dublin, Dec. 15, 2016 (GLOBE NEWSWIRE) -- Research and Markets has announced the addition of the "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026 " report to their offering. The "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026" report provides an extensive study of the current landscape and the growing pipeline of new generation antibiotics targeting drug-resistant bacteria. As indicated earlier, owing to the over-prescription of antibiotics due to improper diagnosis, lack of adherence to proper dosage regimens, their widespread availability as over-the-counter (OTC) drugs, and overuse in agriculture and poultry farming, most antibiotics have been rendered ineffective. Moreover, there currently exists an expanding lag between the pace at which drug resistant bacteria evolve and the time taken for new drugs to reach the market. As a result, antibiotic drug resistance has escalated into a global threat. There are concerns that the lack of effective drugs in this domain may soon trigger the relapse of the pre-antibiotic era, in which individuals died due to day-to-day bacterial infections. According to certain studies, currently, an estimated 700,000 deaths annually are known to occur due to anti-microbial resistance worldwide. In future, the growing threat of antibiotic resistance is anticipated to prove to be more fatal than cancer. The current scenario depicts an urgent need for new antibiotics with novel mechanisms of action, having the ability to combat antibiotic resistance. The US and EU governments have amended their action plans and conducted many conferences to raise awareness about the situation among both experts in the domain and the general public. Such initiatives are addressed to support R&D strategies of companies engaged in the development of drugs to combat antibiotic resistance. Efforts are underway to assist drug developers in their clinical trial design issues, and even the simplification of regulatory pathways to expedite the time to market for such drugs. In addition, such initiatives endorse public-private partnerships in advancing scientific and clinical efforts in this domain, aid the setting up of surveillance programs to track the widespread use of antibiotics and the development of resistance, and track the growing economic burden due to this phenomenon as well. The new generation antibiotics pipeline comprises of several molecules that target infections caused by deadly pathogens classified under ESKAPE or as urgent threats by the CDC. Several start-ups have entered the market and undertaken various initiatives to develop novel antibiotics with unique mechanisms of action. The report features: - An overview of the current state of the market with respect to the key players involved, phase of development of pipeline products (clinical and preclinical/discovery), target classes of pathogens (Gram-negative versus Gram-positive), drug classes and key disease indications. In addition, we have included an insightful representation of the developer landscape, highlighting the geographical presence of key players in the industry. - Detailed profiles of approved drugs, as well as those in phase III of clinical development, highlighting information on clinical trials, their current status of development, recent developments and associated collaborations. - Insights on novel alternative therapies that are being explored/evaluated to target antibiotic resistant pathogenic bacteria; these include teixobactin, anti-microbial peptides, antisense antibacterials, quorum sensing inhibition, nano-metal based therapies and anti-biofilm agents. - Details on the most popular therapeutic areas, namely acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP) Clostridium difficile infections (CDIs), complicated intra-abdominal infections (cIAIs), complicated urinary tract infections (cUTIs) and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). For each indication, we have provided a brief description of the disease, information on its epidemiology, available treatment plans and active comparator studies of approved drug candidates that are prescribed for the aforementioned indications. - An illustrative grid representation and a bulls-eye analysis of the pipeline molecules, based on their development stage, spectrum of activity and the key indications. - Future commercial potential of the market based on a detailed opportunity analysis, for the period between 2016 and 2026. The research, analysis and insights presented in this report include potential sales of approved antibiotics and those in late stages of development. Key Topics Covered: 1. Preface 2. Executive Summary 3. Introduction 4. Antibiotic Drug Resistance: Development Pipeline and Market Landscape 5. Clinical Development Analysis and Key Comparator Studies 6. New Generation Antibiotics: Marketed Drugs 7. New Generation Antibiotics: Phase III Drugs 8. Emerging Therapies to Combat Antibiotic Resistance 9. Key Therapeutic Areas 10. Market Forecast and Opportunity Analysis 11. Conclusion 12. Interview Transcripts 13. Appendix 1: Tabulated Data 14. Appendix 2: List of Companies and Organization - AAIPharma Services - ABAC Therapeutics - ANTABIO - Abbott Laboratories - Abgentis - Absynth Biologics - Achaogen - Acino Holdings - Actavis - Actelion Pharmaceuticals - Adenium Biotech - Adimab - Aequor - AiCuris - Alaxia Pharma - Albany Molecular Research (AMRI) - Allecra Therapeutics - Allergan - Angelini - Antibio Tx - Antibiotic Adjuvant - Aphios - Appili Therapeutics - Arietis Pharma - Arpida - Arsanis - Assembly Biosciences - AstraZeneca - Austell Laboratories - Aventis Pharma - BKG Pharma - BUGWORKS - Basilea Pharmaceutica - Bayer Pharma - BioVersys - Biocidium Biopharmaceuticals - Biocon - Biosearch Italia - Biovertis - Blueberry Therapeutics - C3 Jian - Calixa Therapeutics - Cantab Anti-infectives - Cardiome Pharma - Cellceutix Corporation - Cempra - Cerexa - Clinigen Group - ContraFect - Crestone - Crystal Genomics - Cubist Pharmaceuticals - CyDex Pharmaceuticals - DSM Sinochem Pharmaceuticals - Da Volterra - Daiichi Sankyo - Debiopharm International - Deinove - Demuris - Discuva - Dong Wha Pharmaceuticals - Dong-A Pharmaceutical - Durata Therapeutics - Eli Lilly - Eligo Bioscience - EnBiotix - Entasis Therapeutics - Eurofarma Laboratórios - Evolva Holding - Evotec - Eydo Pharma - FOB Synthesis - Fedora Pharmaceuticals - Forest Laboratories - Fujisawa Pharmaceuticals - GSK - Galapagos - GangaGen - GeneWEAVE - Hikma Pharmaceuticals - IASO Pharma - iNtRON Biotechnology - Immuron - Indel Therapeutics - Institute of Metagenomics and Microbial Technologies (IMMT) - InterMune - Ionis Pharmaceuticals - Isis Pharmaceuticals - Janssen-Ortho - Japan Radio Company - Johnson & Johnson - Kyorin Pharmaceutical - LegoChem Biosciences - Ligand Pharmaceuticals - Lyndra - MGB Biopharma - Macrolide Pharmaceuticals - MarBiLeads - Matinas BioPharma - MedImmune - Meiji Seika Pharma - Melinta Therapeutics - MerLion Pharmaceuticals - Merck - MethylGene - Microbecide - MicuRx Pharmaceuticals - Mirati Therapeutics - Monash University - MorphoSys - Morphochem - Motif Bio - Mutabilis - Nabriva Therapeutics - Naicon - NanoSafe Coatings - Nanotherapeutics - Navigen Pharmaceuticals - Nemesis Bioscience - Nexgen Biosciences - Nobelex Biotech - Northeastern University - Northern Antibiotics - Nosopharm - NovaBiotics - NovaDigm Therapeutics - Novexel - NovoBiotic Pharmaceuticals - Nuprim - OJ-Bio - Optimer Biotechnology - Optimer Pharmaceuticals - Osel - PENDOPHARM - Pacific Beach BioSciences - Par Pharmaceutical - Paratek Pharmaceuticals - Patheon - Peninsula Pharmaceuticals - Peptilogics - Pfizer - Pherecydes Pharma - Phico Therapeutics - Polyphor - Procarta Biosystems - Pure Actives - R-Pharm - RQx Pharmaceuticals - RaQualia Pharma - Rebiotix - Redx Pharma - Rempex Pharmaceuticals - RexC Pharmaceuticals - Rib-X Pharmaceuticals - Roche - Rx3 Pharmaceuticals - Sanofi-Aventis - SciClone Pharmaceuticals - Sequella - Seres Therapeutics - SetLance - Shionogi - Shire - SinSa Labs - Specialised Therapeutics Australia - Spero Therapeutics - Sumitomo Dainippon Pharma (DSP) - Summit Therapeutics - Synamp Pharmaceuticals - Synthetic Biologics - TAXIS Pharmaceuticals - TaiGen Biotechnology - Takeda Pharmaceutical - Talon Pharmaceuticals - Targanta Therapeutics - TechnoPhage - Techulon - Tetraphase Pharmaceuticals - The Medicines Company - TheraBor Pharmaceuticals - Theravance Biopharma - Treat Systems - Trius Therapeutics - University of Michigan Life Sciences Institute - University of Pittsburgh - Vaxdyn - VenatoRx Pharmaceuticals - Versicor Pharmaceuticals - VibioSphen - Vicuron Pharmaceuticals - ViroPharma - Vitas Pharma - Vyome Biosciences - Wakunaga Pharmaceutical - Warner Chillcott - Wockhardt - Yamanouchi Pharmaceutical - Zavante Therapeutics For more information about this report visit http://www.researchandmarkets.com/research/gtt9s3/antibacterial


Stubbings W.,MerLion Pharmaceuticals | Leow P.,MerLion Pharmaceuticals | Yong G.C.,MerLion Pharmaceuticals | Goh F.,MerLion Pharmaceuticals | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Finafloxacin is a novel fluoroquinolone that exhibits enhanced antibacterial activity under acidic conditions. The aim of this study was to define the in vitro pH-activity relationship. Finafloxacin exhibited optimal antibacterial activity between pH 5.0 and 6.0 at which MICs were 4- to 8-fold lower than those determined at neutral pH. These observations were then confirmed against a larger collection of bacteria. These data suggest that finafloxacin could potentially offer a therapeutic advantage within acidic foci of infection. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Emrich N.-C.,University of Hamburg | Heisig A.,University of Hamburg | Stubbings W.,MerLion Pharmaceuticals | Labischinski H.,MerLion Pharmaceuticals | Heisig P.,University of Hamburg
Journal of Antimicrobial Chemotherapy | Year: 2010

Objectives: Finafloxacin is an investigational fluoroquinolone exhibiting broad-spectrum activity that is enhanced under slightly acidic conditions (pH 5.0-6.5). The impact of individual and combinations of chromosomal mutations (gyrA, parC and marR) and the plasmid-mediated fluoroquinolone resistance mechanisms QepA1, QnrA1, QnrB1, QnrS1 and AAC(6′)-Ib-cr were investigated. Methods: The MICs of finafloxacin, compared with those of ciprofloxacin, levofloxacin and moxifloxacin, were determined at pH 5.8 and 7.2. Results: MICs of finafloxacin compared with other fluoroquinolones at pH 5.8 were lower by a factor of 2-256. MICs of finafloxacin were unaffected by QepA1. Moreover, finafloxacin appeared not to be a substrate for AAC(6′)-Ib-cr. Conclusions: Compared with ciprofloxacin, levofloxacin and moxifloxacin, finafloxacin shows higher activity especially at pH 5.8 against Escherichia coli mutants expressing known fluoroquinolone resistance determinants alone and in combinations. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Higgins P.G.,University of Cologne | Stubbings W.,MerLion Pharmaceuticals | Wisplinghoff H.,University of Cologne | Seifert H.,University of Cologne
Antimicrobial Agents and Chemotherapy | Year: 2010

This study compared the activity of finafloxacin, a novel fluoroquinolone which shows enhanced activity under acidic pH, and that of ciprofloxacin against Acinetobacter baumannii under standard conditions (pH 7.2) and at a pH of 5.8. Overall, finafloxacin demonstrated superior activity to ciprofloxacin under acidic conditions. Furthermore, finafloxacin showed comparable activity to ciprofloxacin at pH 7.2. Hence, finafloxacin could be a promising new antimicrobial agent for the treatment of A. baumannii infections at acidic body compartments. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Dalhoff A.,University of Kiel | Stubbings W.,MerLion Pharmaceuticals | Schubert S.,University of Kiel
Antimicrobial Agents and Chemotherapy | Year: 2011

Kill kinetics and MICs of finafloxacin and ciprofloxacin against 34 strains with defined resistance mechanisms grown in cation-adjusted Mueller-Hinton broth (CAMHB) at pH values of 7.2 and 5.8 and in synthetic urine at pH 5.8 were determined. In general, finafloxacin gained activity at low pH values in CAMHB and remained almost unchanged in artificial urine. Ciprofloxacin MICs increased and bactericidal activity decreased strain dependently in acidic CAMHB and particularly in artificial urine. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Sharif S.,Washington University in St. Louis | Kim S.J.,Baylor University | Labischinski H.,MerLion Pharmaceuticals | Chen J.,Washington University in St. Louis | Schaefer J.,Washington University in St. Louis
Journal of Bacteriology | Year: 2013

Peptidoglycan (PG) composition in intact cells of methicillin-resistant Staphylococcus aureus (MRSA) and its isogenic Fem mutants has been characterized by measuring the glycine content of PG bridge structures by solid-state nuclear magnetic resonance (NMR). The glycine content estimated from integrated intensities (rather than peak heights) in the cell walls of whole cells was increased by approximately 30% for the FemA mutant and was reduced by 25% for the FemB mutant relative to expected values for homogeneous structures. In contrast, the expected compositions were observed in isolated cell walls of the same mutants. For FemA mutant whole cells, the increase was due to the presence of triglycyl bridge PG units (confirmed directly by mass spectrometric analysis), which constituted 10% of the total PG. These species were coalesced in some sort of a lattice or aggregate with spatial proximity to other PG bridges. This result suggests that the triglycyl-bridged PG units form a PG-like structure that is not incorporated into the mature cell wall. © 2013, American Society for Microbiology.

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