Reaxys Medicinal Chemistry
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Reaxys Medicinal Chemistry

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

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

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  • Olivier Barberan is currently Senior Product Manager in charge of Reaxys Medicinal Chemistry at Elsevier since beginning 2013. Following a Engineer degree in Chemistry and Biology at EcoleCentrale Marseille in 1996 and a PhD in Therapeutic Chemistry related to VEGF involvement in diabetic retinopathy at the University of Paris XI in 2000, he joined Aureus Sciences and held Project Leader/Project Manager positions for a number of fields including Kinase, GPCR, ADME/DDI. In 2006, he was appointed to a Director of Product Development position. After the acquisition of Aureus Sciences in 2013 by Elsevier, he moved into a new position in Elsevier Life Science group as Senior Product Manager.

Reaxys Medicinal Chemistry Reaxys Medicinal Chemistry Presentation Transcript

  • INTRODUCTION TO REAXYS MEDICINAL CHEMISTRY Webinar presented October 16, 2013 Olivier Barberan Senior Product Manager Your Presenter: Dr. Olivier Barberan Elsevier October 16, 2013 1
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER SITUATION: DRUG DISCOVERY ELN Known ligands Knowledge survey Therapeutic target Chemistry Generate chemistry ideas DBs Check chemical feasibility In-house Analyze SAR Synthesize or buy Report Test Check No single solution will fit all ADME/Tox needs, but… Journals ELN Biology Docs Flatfiles Journals 2
  • In-house Known ligands Knowledge survey Therapeutic target Generate chemistry ideas Analyze SAR Report Chemistry Check chemical feasibility Synthesize or buy Test … is that really being able Wouldn’t 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? Docs 3 Flatfiles ELN
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER AGENDA Elsevier Life science Solution Reaxys Medicinal Chemistry Content coverage Application in Drug discovery QA 4
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER PART OF LIFE SCIENCE SOLUTIONS A SUITE OF INTEROPERABLE, DOMAIN-SPECIFIC, DECISION SUPPORT TOOLS MEDSCAN TEXT MINING TARGETINSIGHTS (CONTENT) INTEGRATION PATHWAY STUDIO PHARMAPENDIUM EMBASE TAXONOMIES QUOSA 5
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER PART OF LIFE SCIENCE SOLUTIONS A SUITE OF INTEROPERABLE, DOMAIN-SPECIFIC, DECISION SUPPORT TOOLS MEDSCAN REAXYS CHEMISTRY DISCOVERY ENGINE REAXYS MEDICINAL CHEMISTRY Combines 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) INTEGRATION PHARMAPENDIUM EMBASE TAXONOMIES QUOSA 6
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER CONTENT COVERAGE 7
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER ESSENTIAL INFORMATION: 100+ EXPERIMENTAL FIELDS Reaxys Medicinal Chemistry excerpts all the relevant Quantitative data
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER 9 ESSENTIAL INFORMATION: SUPPORTING CRITICAL STAGES IN THE DRUG DISCOVERY & DEVELOPMENT PIPELINE COMPUTATIONAL CHEMIST (CADD*) “I need to find hits for druggable targets” (virtual screening) DISCOVERY HIT TO LEAD MEDICINAL CHEMIST PHARMACOLOGIST “I need to optimize chemical structures in order to improve affinity, selectivity ADMET properties and decrease side effects” “I need to define relevant pharmacological models on animals” LEAD OPTIMIZATION COMPUTATIONAL CHEMIST (CADD*) COMPUTATIONAL CHEMIST (CADD*) “I need to optimize affinity and selectivity of hits” (Structure based design QSAR) PRECLINICAL “I need to optimize other pharmaceutical properties while maintaining affinity” (QSPR) DEVELOPMENT SYNTHETIC CHEMIST “I need to define the easiest and most productive way to reach my target compound” PROJECT 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)
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER 10 THE WORLD OF MEDICINAL CHEMISTRY AT YOUR FINGERTIPS REAXYS MEDICINAL CHEMISTRY: THE MOST POWERFUL AND VERSATILE MEDICINAL CHEMISTRY DISCOVERY ENGINE ESSENTIAL INFORMATION • 2.4 M chemical compounds • 9 M biological experimental results • 5100 Pharmacological targets RELEVANT ANSWERS • Chemistry driven searches (Substructure/Similarity) • Pharmacology driven searches (Target, Cell, Bioassay) • Taxonomies-driven searches ACTIONABLE • Intuitive and powerful user-interface • No access barrier • Flexible export (Manageable by user)
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER REAXYS MEDICINAL CHEMISTRY : PATENTS COVERAGE Patents Origin and starting date US : 1971-present EP : 1979-present WO : 1978-present (English only) Patents are coming from the A61K class mainly but not only. Patents count : 50632
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER REAXYS 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.
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER ESSENTIAL INFORMATION COMPOUND CHEMICAL STRUCTURE ,NAME, CODE, SYNONYM OF COMPOUND DRUGGABLE TARGET EXPLORE TARGET AFFINITY PATTERNS OF CHEMICAL COMPOUNDS IN 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, CHONDROGENESIS ANIMAL MODELS DISEASE OVARIECTOMIZED RAT IN OSTEOPOROSIS, TREATMENT OF GLAUCOMA, XENOGRAFTED ANIMALS WITH TUMORS TO TEST AND DEVELOP ANTINEPLASTIC DRUGS PHARMACOKINETIC AND ADME PROPERTIES METABOLIC STABILITY, INTRINSIC CLEARANCE, HALF LIFE OF ELIMINATION, BIOAVAILABILITY, IN VIVO CLEARANCE TOXICITY CYTOTOXICITY, CARDIOTOXICITY, CHRONIC TOXICITY
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER 14 INTERACT WITH YOUR WORKFLOW Link to full text articles Link to Reaxys: ‐ Compounds ‐ Citations Link to full text Patent: Espacenet Link to Drug Bank Link to Uniprot Link to Embase Link to Protein 3D structure: PDB Export data in multiple formats: Text, Excel, SDF, R DF, XML files to be incorporated into third party tools
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER APPLICATION IN DRUG DISCOVERY 15
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER ACCESS TO KNOWLEDGE ALONG DRUG DISCOVERY CHAIN Project 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-activity Compound Library - Focused Library - hERG Model - CYP Model HTS/Virtual Screening - Calcium T Type Channel - Hit Generation : customer story - Phenotypic in silico Screening Hit 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 pathway Lead Optimization - Exploration of structural features of a lead series of Compounds -Safety pharmacology (off Targets) - Pharmacokinetics - ADMET - Computational chemistry and molecular modeling 16
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER PROJECT KICK OFF AKT1 INHIBITORS 17
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER AKT INHIBITORS • AKT 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 cancer • Akt2 is an important signaling molecule in the Insulin signaling pathway • The role of Akt3 is less clear, though it appears to be predominantly expressed in the brain THEREFORE, UNDERSTANDING AKT AND ITS PATHWAYS IS IMPORTANT FOR THE CREATION OF BETTER THERAPIES TO TREAT CANCER AND TUMOR CELLS.
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER ABOUT AKT1 INHIBITORS IN REAXYS MEDICINAL CHEMISTRY • MOST ACTIVE COMPOUNDS ON AKT1 (IC50, KI OR KD BELOW 0.05 µM?) • TARGET SELECTIVITY (AKT1 VERSUS AKT2) • PK OF COMPOUNDS CLASSES • ADVERSE EFFECTS : CYP-BLOCKADE • ADVERSE EFFECT : HERG-ACTIVITY
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER PROJECT KICK OFF LIVE DEMO 20
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER IN 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
  • DR. OLIVIER BARBERAN | SEPTEMBER 2013| ELSEVIER THANK YOU QUESTIONS? 22
  • CLIQUEZ ICI POUR CHANGER LE TEXTE THANK 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-SUPPORT Please fill out the survey that appears on your screen after leaving the webinar. 23