EuropeanScreeningPortChemoinformatic Tools forthe Hit Discovery ProcessEuropean ScreeningPort GmbHBjörn WindshügelMay 29 2...
EuropeanScreeningPortEstablished in 2007Service provider for academics• High-throughput screening• High-content screening•...
EuropeanScreeningPortEstablished in 2007Service provider for academics• High-throughput screening• High-content screening•...
Results handling• Bioactivity• Frequent hitter?• Add. InformationEuropeanScreeningPortHTS at ESPEvotecPoCKiWiZHTSHit ListC...
Screening database handling• ENZO, LOPAC, etc.EuropeanScreeningPortInstant JChem at ESP
Screening database handling• ENZO, LOPAC, etc.IMI project “New Drugs for Bad Bugs”EuropeanScreeningPortInstant JChem at ESP
EuropeanScreeningPortInnovative Medicines InitiativePublic-Private-Partnership• EFPIA• European CommissionBudget: 2 bn EUR...
EuropeanScreeningPort“New Drugs for Bad Bugs”Fight against increasing antimicrobial resistance• Annual treatment and socie...
EuropeanScreeningPortSeveral topics• Topic 1: Clinical trials- COMBACTE• Topic 2: Understanding mech. of bacterial resista...
EuropeanScreeningPort“New Drugs for Bad Bugs”
EuropeanScreeningPortTRANSLOCATIONConsortium members• 5 EFPIA, 1 non-EFPIA, 14 public, 5 SMEsTasks• How potential drugs cr...
EuropeanScreeningPortThe ND4BB Information Centre• Heterogenous data- Legacy data on successful and failed EFPIA programme...
EuropeanScreeningPortTRANSLOCATIONBioassay related studiesCompound Primary, Secondary and Selectivity screeningPathogen pr...
EuropeanScreeningPortData analysis team• Deliver recommendations for future R&D- What factors are common to failed lead op...
EuropeanScreeningPortThank You!
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EUGM 2013 - Björn Windshügel (European ScreeningPort): Chemoinformatic tools for the hit discovery process

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In the drug discovery process high-throughput screening is often applied as initial procedure for the identification of hit molecules against a certain target, e.g. an enzyme or G protein-coupled receptor. In addition, virtual screening campaigns utilizing commercially available compound libraries are often performed that allow the search for potential hit molecules within a much larger chemical space as usually accessible within the in-house compound libraries. Chemoinformatic tools provide the opportunity to assist in the setup of experimental and virtual screening campaigns (e.g. assembly of compound libraries) as well as the analysis of screening results and structures of hit compounds. In this presentation the implementation of ChemAxon tools into the European ScreeningPort workflow will be presented using selected examples from previous and ongoing experimental and virtual screening campaigns.

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EUGM 2013 - Björn Windshügel (European ScreeningPort): Chemoinformatic tools for the hit discovery process

  1. 1. EuropeanScreeningPortChemoinformatic Tools forthe Hit Discovery ProcessEuropean ScreeningPort GmbHBjörn WindshügelMay 29 2013
  2. 2. EuropeanScreeningPortEstablished in 2007Service provider for academics• High-throughput screening• High-content screening• Computational Chemistry~20 peopleProfitable since 3 yearsSuccessful funding procurementESP in a Nutshell
  3. 3. EuropeanScreeningPortEstablished in 2007Service provider for academics• High-throughput screening• High-content screening• Computational Chemistry~20 peopleProfitable since 3 yearsSuccessful funding procurement
  4. 4. Results handling• Bioactivity• Frequent hitter?• Add. InformationEuropeanScreeningPortHTS at ESPEvotecPoCKiWiZHTSHit ListCompound Inhibition (%)ESP-0815 83.2ESP-666 79.3ESP-4711 71.4ESP-27 52.4ESP-13 21.6
  5. 5. Screening database handling• ENZO, LOPAC, etc.EuropeanScreeningPortInstant JChem at ESP
  6. 6. Screening database handling• ENZO, LOPAC, etc.IMI project “New Drugs for Bad Bugs”EuropeanScreeningPortInstant JChem at ESP
  7. 7. EuropeanScreeningPortInnovative Medicines InitiativePublic-Private-Partnership• EFPIA• European CommissionBudget: 2 bn EUR• 50 % EFPIA• 50 % European CommissionMission:Improvement of drug development process bysupporting a more eff. discovery and developmentof better and safer medicines for patients.
  8. 8. EuropeanScreeningPort“New Drugs for Bad Bugs”Fight against increasing antimicrobial resistance• Annual treatment and societal costs: 1.5 bn EUR• Only 2 new classes of antimicrobials in last 30 years• Dev. of novel antibiotics financially not attractive
  9. 9. EuropeanScreeningPortSeveral topics• Topic 1: Clinical trials- COMBACTE• Topic 2: Understanding mech. of bacterial resistance- TRANSLOCATION• Topic 3: Drug discovery (gram-negative bacteria)- in evaluationOverall budget• 360.6 M EUR“New Drugs for Bad Bugs”
  10. 10. EuropeanScreeningPort“New Drugs for Bad Bugs”
  11. 11. EuropeanScreeningPortTRANSLOCATIONConsortium members• 5 EFPIA, 1 non-EFPIA, 14 public, 5 SMEsTasks• How potential drugs cross cell envelope?- New technologies for measuring the molecule transport- Understand the mechanism(s) of resistance• Learning from success and failure- InfoCentrewww.imi.europa.eu/content/translocation
  12. 12. EuropeanScreeningPortThe ND4BB Information Centre• Heterogenous data- Legacy data on successful and failed EFPIA programmes- HTS, H2L and L2C studies, in vitro, in vivo, modelling, etc.- Data from future topics• Only derived data- IC50, MICs, SAR tables, protein structures, study reports• Electronic lab notebook- Going live in JuneTRANSLOCATION
  13. 13. EuropeanScreeningPortTRANSLOCATIONBioassay related studiesCompound Primary, Secondary and Selectivity screeningPathogen profiling results (MIC and Time-Kill analyses etc)Resistance profiling (e.g. from clinical isolates)Toxicity and liability results (Cyto-toxicity etc)In-vitro safety assays (P-450, HERG, Cardiac Ion channel panels)Chemi-informatic analyses (cLog P, TPSA, Ro5 parameters etc)In-vitro ADME studiesPhysico-chemical assessments (solubility, Log P, etc.)Transport assays - Influx (e.g. Mass Spec / Fluorescence)Transport assays Efflux (e.g. Mass Spec, Electrophysiology)Adjuvant related assay resultsProdrug related assay resultsAggregated compound Activity (e.g. Heat maps, SAR tables)Bioassay data (Other)Computational, modelling and SimulationMolecular dynamics resultsTrajectoriesMolecular structure resultsMolecule topology resultsParameter filesScripts and meta-dataChemi-informatic analyses (cLog P, TPSA, Ro5 parameters)Binding modesDiscovery (in-vitro) Structural and Omics related DataGenetic dataProteomic dataTranscriptomic dataProtein structural informationStructural and Omics data (other)Pre-clinicalStudy/Animal Model ProtocolsIn-vivo efficacy resultsIn-vivo biomarker resultsIn-vivo Omics resultsIn-vivo ADME studiesIn-vivo Pharmacokinetic (PK) studiesIn-vivo PharmacoDynamic (PD) studiesModelling of PK events (one compartment / two compartment)General in-vitro modelling (ADME, BBB penetration etc)Findings/Conclusions/Summary DocumentsPre-clinical data (Other)The ND4BB Information Centre• Types of data
  14. 14. EuropeanScreeningPortData analysis team• Deliver recommendations for future R&D- What factors are common to failed lead opt. efforts?- Which tools and procedures to use for identifying leadcandidates to be progressed further?- Best practice for predicting resistance in the clinic- Which animal infection model best predicts clin. outcome?• Hypotheses will be validated• Ph.D. position available- www.screeningport.com/jobsTRANSLOCATION
  15. 15. EuropeanScreeningPortThank You!

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