Uppsala, Sweden
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Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.1.1-5 | Award Amount: 14.64M | Year: 2008

Cys-loop receptors (CLRs) form a superfamily of structurally related neurotransmitter-gated ion channels, comprising nicotinic acetylcholine, glycine, GABA-A/C and serotonin (5HT3) receptors, crucial to function of the peripheral and central nervous system. CLRs cover a wide spectrum of functions, ranging from muscle contraction to cognitive functions. CLR (mal)function is linked to various disorders, including muscular dystrophies, neurodegenerative diseases, e.g. Alzheimers and Parkinsons, and neuropsychiatric diseases, e.g. schizophrenia, epilepsy and addiction. CLRs are potentially important drug targets for treatment of disease. However, novel drug discovery strategies call for in depth understanding of ligand binding sites, the structure-function relationships of these receptors and insight into their actions in the nervous system. NeuroCypres assembles the expertise of leading European laboratories to provide a technology workflow, which enables to embark on this next step in CLR structure and function. A major target of this project is to obtain high-resolution X-ray and NMR structures for CLRs and their complexes with diverse ligands, agonists/antagonists, channel blockers and modulators, which will reveal basic mechanisms of receptor functioning from ligand binding to gating and open new avenues to rational drug design. In addition, the project aims at understanding receptor function in the context of the brain, focusing on receptor biosensors, receptor-protein interactions and transgenic models. This major challenge requires application and development of a multidisciplinary workflow of high-throughput (HT) crystallization and HT-electrophysiology technologies, X-ray analysis, NMR and computational modeling, fragment-based drug design, innovative quantitative methods of interaction-proteomics, sensitive methods for visualization of activity and localization of receptors and studies of in vitro and in vivo function in animal models of disease.


Receive press releases from iHealthcareAnalyst, Inc.: By Email Global Fragment-Based Drug Discovery (FBDD) Market Analysis: Services, End Users, Growth Trends and Forecast to 2020, New Research by iHealthcareAnalyst, Inc. Fragment-Based Drug Discovery Market by Service Type (FBDD and HTS Comparative Analysis, Fragment Screening, Biophysical Techniques, NMR Spectroscopy, DSF Assay, Fluorescence Polarization, Isothermal Titration Calorimetry, X-Ray Crystallography, SPR, Bilayer Interferometry, Mass Spectrometry, Capillary Electrophoresis, Biochemical Assays, Non-Biophysical Techniques, Fragment Optimization), End Users (Academic and Research Institutes, Biopharmaceuticals, CROs) 2016-2020. Maryland Heights, MO, February 22, 2017 --( Browse Fragment-Based Drug Discovery Market by Service Type or Components (Comparative Analysis of FBDD and HTS, Fragment Screening, Biophysical Techniques, NMR Spectroscopy, DSF Assay, Fluorescence Polarization, Isothermal Titration Calorimetry, X-Ray Crystallography, SPR, Bilayer Interferometry, Mass Spectrometry, Capillary Electrophoresis, Biochemical Assays, Non-Biophysical Techniques, Fragment Optimization), and End Users (Academic and Research Institutes, Biopharmaceutical Companies, and CROs) 2016-2020 report at https://www.ihealthcareanalyst.com/report/fragment-based-drug-discovery-market/ Fragment-based lead discovery (FBLD) also known as fragment-based drug discovery (FBDD) is a method used for finding lead compounds as part of the drug discovery process. It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity. The global fragment-based drug discovery market segmentation is based on service types or components (comparative analysis of FBDD and HTS, fragment screening, biophysical techniques, NMR spectroscopy, DSF assay, fluorescence polarization, isothermal titration calorimetry, X-ray crystallography, SPR, bilayer interferometry, mass spectrometry, capillary electrophoresis, biochemical assays, non-biophysical techniques, fragment optimization), and end users (academic and research institutes, biopharmaceutical companies, and CROs). The global fragment-based drug discovery market report provides market size (Revenue USD Million 2013 to 2020), market share, market trends and forecasts growth trends (CAGR%, 2016 to 2020). The global fragment-based drug discovery market research report is further segmented by geography into North America (U.S., Canada), Latin America (Brazil, Mexico, Rest of LA), Europe (U.K., Germany, France, Italy, Spain, Rest of EU), Asia Pacific (Japan, China, India, Rest of APAC), and Rest of the World. The global fragment-based drug discovery market report also provides the detailed market landscape, market drivers, restraints, opportunities), market attractiveness analysis and profiles of major competitors in the global market including company overview, financial snapshot, key products, technologies and services offered, and recent developments. Major players operating in the global fragment-based drug discovery market and included in this report are Astex Pharmaceuticals, Alveus Pharmaceuticals, Beactica AB, Charles River Laboratories International, Inc., Crown Bioscience, Inc., Emerald BioStructures, Evotec A.G., Kinetic Discovery, Proteros Fragments, Structure Based Design, Sygnature Discovery, and Sprint Bioscience AB. To request Table of Contents and Sample Pages of this report visit: https://www.ihealthcareanalyst.com/report/fragment-based-drug-discovery-market/ About Us iHealthcareAnalyst, Inc. is a global healthcare market research and consulting company providing market analysis, and competitive intelligence services to global clients. The company publishes syndicate, custom and consulting grade healthcare reports covering animal healthcare, biotechnology, clinical diagnostics, healthcare informatics, healthcare services, medical devices, medical equipment, and pharmaceuticals. In addition to multi-client studies, we offer creative consulting services and conduct proprietary single-client assignments targeted at client’s specific business objectives, information needs, time frame and budget. Please contact us to receive a proposal for a proprietary single-client study. Contact Us iHealthcareAnalyst, Inc. 2109, Mckelvey Hill Drive, Maryland Heights, MO 63043 United States Email: sales@ihealthcareanalyst.com Website: https://www.ihealthcareanalyst.com Maryland Heights, MO, February 22, 2017 --( PR.com )-- The global fragment-based drug discovery market is estimated to reach USD 650 Million in 2020, growing at a CAGR of 10.6% from 2016 to 2020. Increasing adoption of fragment-based screening programs by most of the major pharmaceutical companies, increasing availability of more assay options in research departments of most pharmaceutical and biotechnology companies for high hit rates of fragment-based screens are the major drivers of the global fragment-based drug discovery market, and are likely continue this trend during the forecast period.Browse Fragment-Based Drug Discovery Market by Service Type or Components (Comparative Analysis of FBDD and HTS, Fragment Screening, Biophysical Techniques, NMR Spectroscopy, DSF Assay, Fluorescence Polarization, Isothermal Titration Calorimetry, X-Ray Crystallography, SPR, Bilayer Interferometry, Mass Spectrometry, Capillary Electrophoresis, Biochemical Assays, Non-Biophysical Techniques, Fragment Optimization), and End Users (Academic and Research Institutes, Biopharmaceutical Companies, and CROs) 2016-2020 report at https://www.ihealthcareanalyst.com/report/fragment-based-drug-discovery-market/Fragment-based lead discovery (FBLD) also known as fragment-based drug discovery (FBDD) is a method used for finding lead compounds as part of the drug discovery process. It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity.The global fragment-based drug discovery market segmentation is based on service types or components (comparative analysis of FBDD and HTS, fragment screening, biophysical techniques, NMR spectroscopy, DSF assay, fluorescence polarization, isothermal titration calorimetry, X-ray crystallography, SPR, bilayer interferometry, mass spectrometry, capillary electrophoresis, biochemical assays, non-biophysical techniques, fragment optimization), and end users (academic and research institutes, biopharmaceutical companies, and CROs).The global fragment-based drug discovery market report provides market size (Revenue USD Million 2013 to 2020), market share, market trends and forecasts growth trends (CAGR%, 2016 to 2020). The global fragment-based drug discovery market research report is further segmented by geography into North America (U.S., Canada), Latin America (Brazil, Mexico, Rest of LA), Europe (U.K., Germany, France, Italy, Spain, Rest of EU), Asia Pacific (Japan, China, India, Rest of APAC), and Rest of the World. The global fragment-based drug discovery market report also provides the detailed market landscape, market drivers, restraints, opportunities), market attractiveness analysis and profiles of major competitors in the global market including company overview, financial snapshot, key products, technologies and services offered, and recent developments.Major players operating in the global fragment-based drug discovery market and included in this report are Astex Pharmaceuticals, Alveus Pharmaceuticals, Beactica AB, Charles River Laboratories International, Inc., Crown Bioscience, Inc., Emerald BioStructures, Evotec A.G., Kinetic Discovery, Proteros Fragments, Structure Based Design, Sygnature Discovery, and Sprint Bioscience AB.To request Table of Contents and Sample Pages of this report visit: https://www.ihealthcareanalyst.com/report/fragment-based-drug-discovery-market/About UsiHealthcareAnalyst, Inc. is a global healthcare market research and consulting company providing market analysis, and competitive intelligence services to global clients. The company publishes syndicate, custom and consulting grade healthcare reports covering animal healthcare, biotechnology, clinical diagnostics, healthcare informatics, healthcare services, medical devices, medical equipment, and pharmaceuticals.In addition to multi-client studies, we offer creative consulting services and conduct proprietary single-client assignments targeted at client’s specific business objectives, information needs, time frame and budget. Please contact us to receive a proposal for a proprietary single-client study.Contact UsiHealthcareAnalyst, Inc.2109, Mckelvey Hill Drive,Maryland Heights, MO 63043United StatesEmail: sales@ihealthcareanalyst.comWebsite: https://www.ihealthcareanalyst.com Click here to view the list of recent Press Releases from iHealthcareAnalyst, Inc.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.84M | Year: 2016

The promise of more efficient lead discovery is fuelling the enthusiasm for fragment-based lead discovery (FBLD). In this approach, highly sensitive biochemical and biophysical screening technologies are being used to detect the low affinity binding of low molecular weight compounds (the so-called fragments) to protein targets that are involved in pathophysiological processes. By investigating the molecular interactions between fragment hit(s) and the target protein, a detailed understanding of the binding event is obtained. This enables the rational and efficient optimisation of the hit fragment. The optimised compounds represent high quality leads for drug development. The necessary FBLD technologies and approaches have emerged mainly from small and specialised biotech companies. At present, FBLD is being adopted throughout pharmaceutical sciences, including by pharmaceutical companies, SMEs and academic research groups. So far, the necessary training that is needed to obtain an holistic view of the possibilities and opportunities that FBLD provides is missing, most likely because the highly multidisciplinary nature of the FBLD work is difficult to capture within one (academic) institute. Therefore, we have established FragNet as a dedicated FBLD training network. The consortium consists of the most prominent pharmaceutical companies, biotech companies and academic groups that have jointly shaped the FBLD research area. FragNet is committed to train 15 ESRs in all facets of FBLD using the combined technologies, skills and knowledge. This will include both research (e.g., technologies on the interface of chemistry and biology) and transferable skill sets (e.g., writing, media training, entrepreneurship and thorough understanding of scientific knowledge transfer). This will enable the ESRs to excel in todays drug discovery and chemical biology programmes that are performed in public and private organisations in the pharmaceutical sciences.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.3.3-1;HEALTH-2007-2.3.3-7 | Award Amount: 1.94M | Year: 2008

Objective: To find and produce novel target compounds against the influenza virus. Influenza A capsid protein is the target since it does not mutate at the same rate as the Hemagglutinin or Neuraminidase proteins. We aim to develop new therapeutic antiviral solutions to combat the disease. Beyond state of the art: The project combines knowledge based design and synthesis of compounds with unique patented image analysis and mathematical algorithm software to find and develop new types of potential antiviral molecules. The expertise and methodology allows for rapid discovery of lead molecules with the potential to provide new classes of drugs/vaccines which are less sensitive to viral mutation or reassortment. Work plan: Key molecules with optimal binding kinetics to the Influenza capsid protein will be designed and synthesized then analysed and tested in two separate experimental systems for their effect upon the virus structure and maturation process. The evaluation of novel lead drugs will be performed using a combination of new rapid image analysis, backed up by established viral analysis techniques. Finally a plan will be created for the continued verification and development of the lead molecules. Impact: We aim to produce a new class of antiviral drug candidates which specifically bind to influenza A capsid protein. These substances may have two potential effects; 1. Binding could inhibit important protein-protein interactions thereby inhibit virus formation. 2. Binding to the capsid protein could change the virus structure or stabilize the virus particle, resulting in non-infectious particles to which the hosts immune system could respond. The expected impact will be i) identification of targets against influenza to provide new therapeutic options ii) new opportunities to develop an anti-influenza vaccine which might help prevent an influenza pandemic, iii) to support the continued commercial development of the two SME partners.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.3.3-4 | Award Amount: 7.82M | Year: 2010

Influenza viruses cause a highly contagious respiratory disease in both humans and animals. Typically, influenza spreads worldwide in seasonal epidemics resulting in an estimated 3 to 5 million cases of severe illness and 250,000 to 500,000 deaths annually. In addition to these seasonal epidemics there have been several pandemics since the early 1900s, where highly virulent strains emerged, the most devastating being the Spanish Flu of 1918, which caused 20-40 million deaths globally. Vaccination is currently the primary means of controlling the spread of influenza virus infections but due to the viruss notorious ability to mutate, new vaccines must be developed each year. There are a few antiviral drugs that are currently on the market; however, their therapeutic potential is restricted through rapid appearance of drug-resistant viruses during treatment. Thus, the need for novel effective drugs against influenza is evident. The FLUCURE project aims at developing innovative, first-in-class therapeutics against influenza by targeting the viral ribonucleoprotein complex, which is replication core of the virion and a major contributor to viral virulence. The high level of conservation combined with slow mutation rates of the ribonucleoprotein complex should result in therapeutics with broad viral strain specificity associated with a reduced risk for developing resistance. FLUCURE builds further on two successful EU-FP7 drug discovery projects, FLUINHIBIT and FluDrugStrategy, both targeting specific but different protein-protein interactions of the viral ribonucleoprotein complex with small molecule inhibitors. A consortium of 10 partners with the required complementary skills will progress the lead candidates from these two projects synergistically through lead optimization and preclinical development phases, with the final objective to deliver one or more drug candidates suitable for entering clinical development within 4 years.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.32M | Year: 2009

Brain disorders, in particular neurodegenerative diseases and mental illnesses are among the most prevalent and debilitating diseases. Because they are chronic, quality of life and socio-economic prospects are dramatically impaired. Increased life expectancy further enhances the impact of brain dysfunction on society. In coming decades this burden will grow into one of most pressing and costly problems of the EU. Prevalent brain disorders are typically caused by the interplay of environmental factors and genetic variation in multiple genes, which is currently being mapped by large international efforts. Future brain research should aim at integrative projects as a next step to characterize complex interplay between these multiple genetic and environmental factors to reveal how this translates into disease. To succeed, a new generation of neuroscientists is needed, capable of integrating information across different levels, from genes and proteins to synapses, and from networks up to complex brain (dys)function. Eight leading EU institutes (Amsterdam, London, Paris, Heidelberg, Stockholm, Magdeburg, Leuven and Trieste) together with the Japanese RIKEN, five commercial partners and FENS have formed BrainTrain ITN. Partners were selected on their outstanding publication records and ability to integrate different disciplines. BrainTrain builds on our knowledge of genome information and exploits innovative technologies and infrastructure to integrate this to unravel the (dys)function of living neurons, networks and the whole brain. Local specialists offer network-wide training and meetings. Our existing EU funded resources (IP EUsynapse, NeuroCypres and Neuromics EST) will provide an excellent, multicultural and inspiring environment for a new generation of integrative neuroscientists. BrainTrain will deliver 15 skilled ESR prepared for future challenges in neuroscience with optimal career opportunities and the ability to contribute to the fight against brain disorders.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.2-1 | Award Amount: 14.33M | Year: 2010

Major disorders of the Central Nervous System (CNS) affect one in three people in the developed world, often seriously disable the affected individual, and together account for the single largest burden on the healthcare systems of the EU. Most of these disorders act at the neuronal synapse, a cellular organelle comprising in the order of 2000 proteins. Pleiotropy, cross-talk between proteins and the complexity of the underlying signalling complexes pose a significant challenge to dissecting the molecular mechanisms of disease and to design efficient drugs. SynSys assembles leading European laboratories to provide the expertise and established research platforms that uniquely enable a systems-level analysis of synaptic signalling. The consortium features a closed loop from data integration and modelling, human genetics, physiology, proteomics and the application of engineered model systems to test model predictions. The main objectives of this project are to (i) provide a qualitative and quantitative description of the protein composition and the interactome of the mammalian glutamatergic synapse that integrates known human variation in these genes, (ii) to generate quantitative dynamic models describing the main functional features of the synaptic system, (iii) to reiterate on modeling by relating model predictions to synaptic function, (iv) to identify and validate, using appropriate model systems, human vulnerability genes that may form the basis of future therapies. Only a Systems level analysis can provide the means to describe synaptic transmission from molecule to function, its dynamics in relation to physiology and, brain function and brain disorders. As such, SynSys will establish a new platform for iterative molecular analysis of synapse function and dynamic modeling, with the perspective to generate a blueprint for discovery of novel pathways and targets that enable rational strategies to design therapies for human brain disease.


Geitmann M.,Beactica AB | Elinder M.,Uppsala University | Seeger C.,Beactica AB | Seeger C.,Uppsala University | And 4 more authors.
Journal of Medicinal Chemistry | Year: 2011

A novel scaffold inhibiting wild type and drug resistant variants of human immunodeficiency virus type 1 reverse transcriptase (HIV-1RT) has been identified in a library consisting of 1040 fragments. The fragments were significantly different from already known non-nucleoside reverse transcriptase inhibitors (NNRTIs), as indicated by a Tversky similarity analysis.Ascreening strategy involvingSPRbiosensor-based interaction analysis and enzyme inhibition was used. Primary biosensor-based screening, using short concentration series,was followed by analysis of nevirapine competition and enzyme inhibition, thus identifying inhibitory fragments binding to the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding site. Ten hits were discovered, and their affinities and resistance profiles were evaluated with wild type and three drug resistant enzyme variants (K103N, Y181C, and L100I). One fragment exhibited submillimolar K D and IC 50 values against all four tested enzyme variants. A substructure comparison between the fragment and 826 structurally diverse published NNRTIs confirmed that the scaffold was novel. The fragment is a bromoindanone with a ligand efficiency of 0.42 kcal/mol -1. © 2011 American Chemical Society.


Brandt P.,Beactica AB | Geitmann M.,Beactica AB | Danielson U.H.,Beactica AB | Danielson U.H.,Uppsala University
Journal of Medicinal Chemistry | Year: 2011

This study has taken a closer look at the theoretical basis for protein-fragment interactions. The approach involved the deconstruction of 3 non-nucleoside inhibitors of HIV-1 reverse transcriptase and investigation of the interaction between 21 substructures and the enzyme. It focused on the concept of ligand efficiency and showed that ligand independent free energy fees (δG ind) are crucial for the understanding of the binding affinities of fragments. A value of 7.0 kcal mol -1 for the δG ind term is shown to be a lower limit for the NNRTI binding pocket of HIV-1 RT. The addition of theδG ind term to the dissociation free energy in the calculation of a corrected ligand efficiency, in combination with the lack of an efficient ligand binding hot spot in the NNIBP, fully explains the existence of nonbinding NNRTI substructures. By applying the concept to a larger set of ligands, we could define a binding site profile that indicates the absence of an efficient fragment binding hot spot but an efficient binding of fullsized NNRTIs. The analysis explains some of the challenges in identifying fragments against flexible targets involving conformational changes and how fragments may be prioritized. © 2011 American Chemical Society.


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