News Article | November 21, 2016
ReportsnReports.com adds "Tuberculosis - Pipeline Review, H2 2016" to its store providing comprehensive information on the therapeutics under development for Tuberculosis (Respiratory), complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The guide covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Complete report on H2 2016 pipeline review of Tuberculosis with 108 market data tables and 17 figures, spread across 393 pages is available at http://www.reportsnreports.com/reports/755901-tuberculosis-pipeline-review-h2-2016.html. Tuberculosis, commonly known as TB, is a bacterial infection that can spread through the lymph nodes and bloodstream to any organ in body. It is most often found in the lungs. The symptoms of tuberculosis range from no symptoms (latent tuberculosis) to symptoms of active disease. Symptoms include overall sensation of feeling unwell; cough, possibly with bloody mucus, fatigue, shortness of breath, weight loss and pain in the chest. Companies discussed in this Tuberculosis Pipeline Review, H2 2016 report include Abera Bioscience AB, Akthelia Pharmaceuticals Limited, Alvogen Korea Co., Ltd., Anacor Pharmaceuticals, Inc., Archivel Farma S.L., AstraZeneca Plc, Beech Tree Labs, Inc., BioDiem Ltd, BioLingus AG, Biomar Microbial Technologies, Bioversys AG, Celgene Corporation, Cellceutix Corporation, Chongqing Zhifei Biological Products Co., Ltd., Crestone, Inc., Dafra Pharma International Ltd., Daiichi Sankyo Company, Limited, Demuris Limited, Eisai Co., Ltd., Eli Lilly and Company, Ensol Biosciences Inc., EpiVax, Inc., FIT Biotech Oy, GangaGen Inc., GlaxoSmithKline Plc, Globeimmune, Inc., Hager Biosciences, LLC, Hsiri Therapeutics LLC, Imaxio SA, Immunitor, Inc., ImmunoBiology Limited, Inovio Pharmaceuticals, Inc., Johnson & Johnson, Lakewood-Amedex Inc, Lipotek Pty Ltd., Matinas BioPharma Holdings, Inc., Microbion Corporation, Microbiotix, Inc., NEARMEDIC PLUS, Ltd, Novartis AG, NovoBiotic Pharmaceuticals, LLC, Otsuka Holdings Co., Ltd., QureTech Bio AB, Recce Pty Ltd, Rodos BioTarget GmbH, Sanofi, Sanofi Pasteur SA, Sarepta Therapeutics, Inc., Sequella, Inc., Shionogi & Co., Ltd., Sphaera Pharma Pvt. Ltd., Spring Bank Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited, TetraLogic Pharmaceuticals, TGV-Laboratories, Theravectys SA, Tomegavax, Inc., Transgene SA, TVAX Biomedical, Inc., Univalue Valorizacion, S.L., Vaccibody AS, Vakzine Projekt Management GmbH, Vaxil Bio Therapeutics Ltd. and Vichem Chemie Research Ltd. The Tuberculosis (Infectious Disease) pipeline guide also reviews of key players involved in therapeutic development for Tuberculosis and features dormant and discontinued projects. The guide covers therapeutics under Development by Companies /Universities /Institutes, the molecules developed by Companies in Pre-Registration, Phase III, Phase II, Phase I, Preclinical, Discovery and Unknown stages are 1, 5, 7, 8, 61, 37 and 3 respectively. Similarly, the Universities portfolio in Phase III, Phase II, Phase I, Preclinical and Discovery stages comprises 2, 4, 5, 35 and 37 molecules, respectively. Tuberculosis (Infectious Disease) pipeline guide helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. The guide is built using data and information sourced from Global Markets Direct’s proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Scope of this report: The report provides a snapshot of the global therapeutic landscape of Tuberculosis and reviews pipeline therapeutics for Tuberculosis by companies and universities/research institutes based on information derived from company and industry-specific sources and key players involved Tuberculosis therapeutics and enlists all their major and minor projects. The research covers pipeline products based on various stages of development ranging from pre-registration till discovery and undisclosed stages. The report features descriptive drug profiles for the pipeline products which includes, product description, descriptive MoA, R&D brief, licensing and collaboration details & other developmental activities and assesses Tuberculosis therapeutics based on drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report summarizes all the dormant and discontinued pipeline projects with latest news related to pipeline therapeutics for Tuberculosis. ReportsnReports.com is your single source for all market research needs. Our database includes 500,000+ market research reports from over 100+ leading global publishers & in-depth market research studies of over 5000 micro markets. With comprehensive information about the publishers and the industries for which they publish market research reports, we help you in your purchase decision by mapping your information needs with our huge collection of reports. Connect With Us on: Facebook: https://www.facebook.com/ReportsnReports/ LinkedIn: https://www.linkedin.com/company/reportsnreports Twitter: https://twitter.com/marketsreports G+ / Google Plus: https://plus.google.com/111656568937629536321/posts RSS/Feeds: http://www.reportsnreports.com/feed/l-latestreports.xml
Rybniker J.,Ecole Polytechnique Federale de Lausanne |
Rybniker J.,University of Cologne |
Chen J.M.,Ecole Polytechnique Federale de Lausanne |
Sala C.,Ecole Polytechnique Federale de Lausanne |
And 14 more authors.
Cell Host and Microbe | Year: 2014
Mtb EsxA secretion can be targeted in high-throughput screensSmall molecules abrogate EsxA secretion and reduce intracellular bacterial loadsInhibitor BTP15 targets kinase MprB that indirectly regulates ESX-1BBH7 affects Mtb ion homeostasis, revealing a role for zinc stress in ESX-1 regulation © 2014 Elsevier Inc.
Haas D.A.,Hannover Medical School |
Bala K.,Hannover Medical School |
Busche G.,Hannover Medical School |
Weidner-Glunde M.,Hannover Medical School |
And 11 more authors.
PLoS Pathogens | Year: 2013
Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al.
Simon-Szabo L.,Semmelweis University |
Kokas M.,Semmelweis University |
Mandl J.,Semmelweis University |
Keri G.,Semmelweis University |
And 2 more authors.
PLoS ONE | Year: 2014
Lipotoxicity refers to cellular dysfunctions caused by elevated free fatty acid levels playing a central role in the development and progression of obesity related diseases. Saturated fatty acids cause insulin resistance and reduce insulin production in the pancreatic islets, thereby generating a vicious cycle, which potentially culminates in type 2 diabetes. The underlying endoplasmic reticulum (ER) stress response can lead to even β-cell death (lipoapoptosis). Since improvement of β-cell viability is a promising anti-diabetic strategy, the protective effect of metformin, a known insulin sensitizer was studied in rat insulinoma cells. Assessment of palmitate-induced lipoapoptosis by fluorescent microscopy and by detection of caspase-3 showed a significant decrease in metformin treated cells. Attenuation of β-cell lipotoxicity was also revealed by lower induction/activation of various ER stress markers, e.g. phosphorylation of eukaryotic initiation factor 2α (eIF2α), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1) and induction of CCAAT/enhancer binding protein homologous protein (CHOP). Our results indicate that the β-cell protective activity of metformin in lipotoxicity can be at least partly attributed to suppression of ER stress. © 2014 Simon-Szabó et al.
Herrero A.,University of Cantabria |
Pinto A.,University of Cantabria |
Colon-Bolea P.,University of Cantabria |
Casar B.,University of Cantabria |
And 19 more authors.
Cancer Cell | Year: 2015
Nearly 50% of human malignancies exhibit unregulated RAS-ERK signaling; inhibiting it is a valid strategy for antineoplastic intervention. Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling. Here, we describe a small molecule inhibitor for ERK dimerization that, without affecting ERK phosphorylation, forestalls tumorigenesis driven by RAS-ERK pathway oncogenes. This compound is unaffected by resistance mechanisms that hamper classical RAS-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two understudied concepts in cancer therapy: (1) the blockade of sub-localization-specific sub-signals, rather than total signals, as a means of impeding oncogenic RAS-ERK signaling and (2) targeting regulatory protein-protein interactions, rather than catalytic activities, as an approach for producing effective antitumor agents. Herrero et al. identify a small molecule inhibitor of ERK dimerization that impedes the growth of tumor cells dependent on a hyperactivated RAS-ERK pathway. Importantly, the antitumor effect of this compound in cells is not affected by the reported resistance mechanisms for the current BRAF and MEK inhibitors. © 2015 Elsevier Inc.
Kubisch J.,Eötvös Loránd University |
Turei D.,Eötvös Loránd University |
Turei D.,Semmelweis University |
Foldvari-Nagy L.,Eötvös Loránd University |
And 7 more authors.
Seminars in Cancer Biology | Year: 2013
Autophagy, a highly regulated self-degradation process of eukaryotic cells, is a context-dependent tumor-suppressing mechanism that can also promote tumor cell survival upon stress and treatment resistance. Because of this ambiguity, autophagy is considered as a double-edged sword in oncology, making anti-cancer therapeutic approaches highly challenging. In this review, we present how systems-level knowledge on autophagy regulation can help to develop new strategies and efficiently select novel anti-cancer drug targets. We focus on the protein interactors and transcriptional/post-transcriptional regulators of autophagy as the protein and regulatory networks significantly influence the activity of core autophagy proteins during tumor progression. We list several network resources to identify interactors and regulators of autophagy proteins. As in silico analysis of such networks often necessitates experimental validation, we briefly summarize tractable model organisms to examine the role of autophagy in cancer. We also discuss fluorescence techniques for high-throughput monitoring of autophagy in humans. Finally, the challenges of pharmacological modulation of autophagy are reviewed. We suggest network-based concepts to overcome these difficulties. We point out that a context-dependent modulation of autophagy would be favored in anti-cancer therapy, where autophagy is stimulated in normal cells, while inhibited only in stressed cancer cells. To achieve this goal, we introduce the concept of regulo-network drugs targeting specific transcription factors or miRNA families identified with network analysis. The effect of regulo-network drugs propagates indirectly through transcriptional or post-transcriptional regulation of autophagy proteins, and, as a multi-directional intervention tool, they can both activate and inhibit specific proteins in the same time. The future identification and validation of such regulo-network drug targets may serve as novel intervention points, where autophagy can be effectively modulated in cancer therapy. © 2013 Published by Elsevier Ltd.
Toth G.,Hungarian Academy of Sciences |
Baska F.,Vichem Chemie Research Ltd. |
Baska F.,Semmelweis University |
Schretner A.,Hungarian Academy of Sciences |
And 2 more authors.
European Biophysics Journal | Year: 2013
Interactions between thyroid hormone α and β receptors and the eight protonation microspecies of each of the main thyroid hormones (thyroxine, liothyronine, and reverse liothyronine) were investigated and quantitated by molecular modeling. Flexible docking of the various protonation forms of thyroid hormones and high-affinity thyromimetics to the two thyroid receptors was carried out. In this method the role of the ionization state of each basic site could be studied in the composite process of molecular recognition. Our results quantitate at the molecular level how the ionization state and the charge distribution influence the protein binding. The anionic form of the carboxyl group (i.e., carboxylate site) is essential for protein binding, whereas the protonated form of amino group worsens the binding. The protonation state of the phenolate plays a less important role in the receptor affinity; its protonation, however, alters the electron density and the concomitant stacking propensity of the aromatic rings, resulting in a different binding score. The combined results of docking and microspeciation studies show that microspecies with the highest concentration at the pH of blood are not the strongest binding ones. The calculated binding free energy values can be well interpreted in terms of the interactions between the actual sites of the microspecies and the receptor amino acids. Our docking results were validated and compared with biological data from the literature. Since the thyroid hormone receptors influence several physiologic functions, such as metabolic rate, cholesterol and triglyceride levels, and heart frequency, our binding results provide a molecular basis for drug design and development in related therapeutic indications. © 2013 European Biophysical Societies' Association.
PubMed | Leiden University, OcellO B.V., Semmelweis University and Vichem Chemie Research Ltd.
Type: Journal Article | Journal: Journal of biomolecular screening | Year: 2016
3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools were developed to process 3D image data to measure over 800 phenotypic parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the phenotypic profiles induced by their respective ligands, hepatocyte growth factor and EGF. The screening method was applied to a novel collection of 80 putative inhibitors of c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of c-Met, EGFR, or bispecific inhibition of both targets. In conclusion, we describe a fully scalable high-content screening platform that uses phenotypic profiling to discriminate selective and nonselective (off-target) inhibitors in a physiologically relevant 3D cell culture setting.
PubMed | University of Cologne, University of Zaragoza, Alere San Diego, University of Cape Town and 5 more.
Type: Journal Article | Journal: Molecular microbiology | Year: 2016
There is an urgent need to discover new anti-tubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that has potent, bactericidal activity against M. tuberculosis. Mutations in APYS1-resistant M. tuberculosis mapped exclusively to wag31, a gene that encodes a scaffolding protein thought to orchestrate cell elongation. Recombineering confirmed that a Gln201Arg mutation in Wag31 was sufficient to cause resistance to APYS1, however, neither overexpression nor conditional depletion of wag31 impacted M. tuberculosis susceptibility to this compound. In contrast, expression of the wildtype allele of wag31 in APYS1-resistant M. tuberculosis was dominant and restored susceptibility to APYS1 to wildtype levels. Time-lapse imaging and scanning electron microscopy revealed that APYS1 caused gross malformation of the old pole of M. tuberculosis, with eventual lysis. These effects resembled the morphological changes observed following transcriptional silencing of wag31 in M. tuberculosis. These data show that Wag31 is likely not the direct target of APYS1, but the striking phenotypic similarity between APYS1 exposure and genetic depletion of Wag31 in M. tuberculosis suggests that APYS1 might indirectly affect Wag31 through an as yet unknown mechanism.
PubMed | United St Istvan And St Laszlo Hospital, Vichem Chemie Research Ltd, Semmelweis University and Max Planck Institute of Biochemistry
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2016
Activation of various interacting stress kinases, particularly the c-Jun N-terminal kinases (JNK), and a concomitant phosphorylation of insulin receptor substrate 1 (IRS-1) at serine 307 play a central role both in insulin resistance and in -cell dysfunction. IRS-1 phosphorylation is stimulated by elevated free fatty acid levels through different pathways in obesity. A series of novel pyrido[2,3-d]pyrimidin-7-one derivatives were synthesized as potential antidiabetic agents, preventing IRS-1 phosphorylation at serine 307 in a cellular model of lipotoxicity and type 2 diabetes.