reaxys medicinal chemistry

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These are the slides for the Reaxys Medicinal Chemistry webinar that was held on October 16, 2013.


  • 1. INTRODUCTION TO REAXYS MEDICINAL CHEMISTRYWebinar presented October 16, 2013Olivier Barberan Senior Product Manager Your Presenter: Dr. Olivier BarberanElsevier October 16, 2013 1

2. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERSITUATION: DRUG DISCOVERY ELN Known ligands Knowledge surveyTherapeutic targetChemistryGenerate chemistry ideasDBsCheck chemical feasibility In-houseAnalyze SARSynthesize or buyReportTest CheckNo single solution will fit all ADME/Tox needs, butJournalsELNBiologyDocs FlatfilesJournals2 3. In-houseKnown ligands Knowledge surveyTherapeutic targetGenerate chemistry ideasAnalyze SARReportChemistry Check chemical feasibilitySynthesize or buyTest is that really being able Wouldnt it be nicenecessary? to Check switch seamlessly between scientific ADME/Tox Hows about interoperability and domains andintegration? find data that you have Biology not even thought about, but would be important?Docs3FlatfilesELN 4. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERAGENDA Elsevier Life science Solution Reaxys Medicinal Chemistry Content coverage Application in Drug discoveryQA4 5. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERPART OF LIFE SCIENCE SOLUTIONS A SUITE OF INTEROPERABLE, DOMAIN-SPECIFIC, DECISION SUPPORT TOOLSMEDSCANTEXT MININGTARGETINSIGHTS(CONTENT) INTEGRATIONPATHWAY STUDIOPHARMAPENDIUMEMBASETAXONOMIESQUOSA5 6. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERPART OF LIFE SCIENCE SOLUTIONS A SUITE OF INTEROPERABLE, DOMAIN-SPECIFIC, DECISION SUPPORT TOOLSMEDSCAN REAXYS CHEMISTRY DISCOVERY ENGINEREAXYS MEDICINAL CHEMISTRYCombines relevant chemistry information from 16,000 periodicals and over 500m TARGETINSIGHTS experimentally validated facts with synthesis planning functionality.Identify, optimize and prioritize compounds with optimum PATHWAY STUDIO affinity, selectivity and ADMET properties.(CONTENT) INTEGRATIONPHARMAPENDIUMEMBASETAXONOMIESQUOSA6 7. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERCONTENT COVERAGE7 8. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERESSENTIAL INFORMATION: 100+ EXPERIMENTAL FIELDSReaxys Medicinal Chemistry excerpts all the relevant Quantitative data 9. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER 9ESSENTIAL INFORMATION: SUPPORTING CRITICAL STAGES IN THE DRUG DISCOVERY & DEVELOPMENT PIPELINE COMPUTATIONAL CHEMIST (CADD*) I need to find hits for druggable targets (virtual screening)DISCOVERYHIT TO LEADMEDICINAL CHEMISTPHARMACOLOGISTI need to optimize chemical structures in order to improve affinity, selectivity ADMET properties and decrease side effectsI need to define relevant pharmacological models on animalsLEAD OPTIMIZATIONCOMPUTATIONAL CHEMIST (CADD*)COMPUTATIONAL CHEMIST (CADD*)I need to optimize affinity and selectivity of hits (Structure based design QSAR)PRECLINICALI need to optimize other pharmaceutical properties while maintaining affinity (QSPR)DEVELOPMENTSYNTHETIC CHEMIST I need to define the easiest and most productive way to reach my target compoundPROJECT MANAGER I need to be up to date with regards to competitors working on the same subjects (Which compounds, targets are published in Journals and/or patents) 10. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER 10THE WORLD OF MEDICINAL CHEMISTRY AT YOUR FINGERTIPS REAXYS MEDICINAL CHEMISTRY: THE MOST POWERFUL AND VERSATILE MEDICINAL CHEMISTRY DISCOVERY ENGINEESSENTIAL INFORMATION 2.4 M chemical compounds 9 M biological experimental results 5100 Pharmacological targetsRELEVANT ANSWERS Chemistry driven searches (Substructure/Similarity) Pharmacology driven searches (Target, Cell, Bioassay) Taxonomies-driven searchesACTIONABLE Intuitive and powerful user-interface No access barrier Flexible export (Manageable by user) 11. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERREAXYS MEDICINAL CHEMISTRY : PATENTS COVERAGEPatents Origin and starting dateUS : 1971-present EP : 1979-present WO : 1978-present (English only) Patents are coming from the A61K class mainly but not only.Patents count : 50632 12. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERREAXYS MEDICINAL CHEMISTRY : JOURNALS COVERAGE 206421 articles are included in Reaxys Medicinal Chemistry corresponding to 1047 Journals from 1980 to present. Some articles stored in Reaxys Medicinal Chemistry are older than 1980. 1000 articles spread between 1979 and 1941. 13. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERESSENTIAL INFORMATION COMPOUND CHEMICAL STRUCTURE ,NAME, CODE, SYNONYM OF COMPOUNDDRUGGABLE TARGET EXPLORE TARGET AFFINITY PATTERNS OF CHEMICAL COMPOUNDSIN VITRO AND CELL BASED ASSAYS IN VITRO ASSAYS (BINDING, SECOND MESSENGER ETC..) AND CELL BASED ASSAYS FOR EXAMPLE : AGGREGATION, ANGIOGENESIS, APOPTOSIS, CELL DIFFERENTIATION, CELLULAR CYCLE, CHONDROGENESISANIMAL MODELS DISEASE OVARIECTOMIZED RAT IN OSTEOPOROSIS, TREATMENT OF GLAUCOMA, XENOGRAFTED ANIMALS WITH TUMORS TO TEST AND DEVELOP ANTINEPLASTIC DRUGSPHARMACOKINETIC AND ADME PROPERTIES METABOLIC STABILITY, INTRINSIC CLEARANCE, HALF LIFE OF ELIMINATION, BIOAVAILABILITY, IN VIVO CLEARANCETOXICITY CYTOTOXICITY, CARDIOTOXICITY, CHRONIC TOXICITY 14. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER 14INTERACT WITH YOUR WORKFLOWLink to full text articlesLink to Reaxys: Compounds CitationsLink to full text Patent: EspacenetLink to Drug BankLink to UniprotLink to EmbaseLink to Protein 3D structure: PDBExport data in multiple formats: Text, Excel, SDF, R DF, XML files to be incorporated into third party tools 15. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERAPPLICATION IN DRUG DISCOVERY15 16. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERACCESS TO KNOWLEDGE ALONG DRUG DISCOVERY CHAINProject Kick off- Indications for target - Compound active on target - Most active compounds (IC50, Ki, EC50 < 50nM) - Most active competitors - Target selectivity - PK of Compounds classes - Adverse effects : CYPblockade - Adverse effect : hERG-activityCompound Library- Focused Library - hERG Model - CYP ModelHTS/Virtual Screening- Calcium T Type Channel - Hit Generation : customer story - Phenotypic in silico ScreeningHit to Lead- High affinity towards the target - Show selectivity versus targets - Reduce binding to HSA - Improve cell permeability - Not be metabolized rapidly - Not interfere with the P450 enzymes -Not interfere with the Pgp - Show selectivity versus targets (Advanced) - Multiple inhibitors : Renin angiotensin pathwayLead Optimization- Exploration of structural features of a lead series of Compounds -Safety pharmacology (off Targets) - Pharmacokinetics - ADMET - Computational chemistry and molecular modeling16 17. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERPROJECT KICK OFF AKT1 INHIBITORS17 18. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERAKT INHIBITORSAKT IS ASSOCIATED WITH TUMOR CELL SURVIVAL, PROLIFERATION, AND INVASIVENESS.THE ACTIVATION OF AKT IS ALSO ONE OF THE MOST FREQUENT ALTERATIONS OBSERVED IN HUMAN CANCER AND TUMOR CELLS.Akt1 has been implicated as a major factor in many types of cancerAkt2 is an important signaling molecule in the Insulin signaling pathwayThe role of Akt3 is less clear, though it appears to be predominantly expressed in the brainTHEREFORE, UNDERSTANDING AKT AND ITS PATHWAYS IS IMPORTANT FOR THE CREATION OF BETTER THERAPIES TO TREAT CANCER AND TUMOR CELLS. 19. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERABOUT AKT1 INHIBITORS IN REAXYS MEDICINAL CHEMISTRY MOST ACTIVE COMPOUNDS ON AKT1 (IC50, KI OR KD BELOW 0.05 M?) TARGET SELECTIVITY (AKT1 VERSUS AKT2) PK OF COMPOUNDS CLASSES ADVERSE EFFECTS : CYP-BLOCKADE ADVERSE EFFECT : HERG-ACTIVITY 20. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERPROJECT KICK OFF LIVE DEMO20 21. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERIN SUMMARY Reaxys Medicinal Chemistry is a Powerful solutions across the entire Drug Discovery Workflow Designed to help Medicinal and Computational Chemists in all sectors, advance more quickly and confidently through their research.21 22. DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIERTHANK YOUQUESTIONS?22 23. CLIQUEZ ICI POUR CHANGER LE TEXTETHANK YOU FOR MORE INFORMATION AND QUESTIONS PLEASE USE THE CONTACT DETAILS ON OUR ONLINE PAGE. OUR NEXT REAXYS WEBINAR IS ON OCTOBER 22. AND YOU MAY ALSO BE INTERESTED IN JOINING OUR REAXYS WEBINARS. ALL WEBINARS MAY BE FOUND ON OUR WEBINAR PAGE ALL TRAINING AND SUPPORT MATERIALS ARE LOCATED AT WWW.ELSEVIER.COM/ONLINE-TOOLS/REAXYS/CUSTOMER-SUPPORTPlease fill out the survey that appears on your screen after leaving the webinar. 23


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