Piotr Golkiewicz Life Sciences Solutions Consultant Central-Eastern Europe
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PIOTR GOLKIEWICZ LIFE SCIENCES SOLUTIONS CONSULTANT CENTRAL-EASTERN EUROPE 1 SERVING THE LIFE SCIENCES SPACE ADDRESSING KEY CHALLENGES ACROSS THE R&D VALUE CHAIN Characterize Characterize & discover Translate preclinical Monitor drug adverse targets & analyze molecules data in humans events & disease pathways Identify & confirm lead (Translational) real-world evidence compounds data in literature Drug Candidate Preclinical Data Selection Go-No Go Decision Validation Managing risk Discovery Pre-clinical Clinical Post-launch Broader full-text indexing Text Mining & Data Integration Integrate the world of biomedical content of data & solutions Search full-text, peer- Largest database for access reviewed journal articles to abstract & citation data 2 WHAT’S IN A TYPICAL CHEMISTRY DOCUMENT (PUBLICATION OR PATENT)? Scientific topic, author Chemical reactions Can be searched in full Cannot be searched by text, but difficult to find text terms in full text the right search term Can be searched in full text, but you don’t want to read the whole paper in you are interested only by this section! Experimental procedures Cannot be searched by Cannot be searched by Cannot be searched by text terms in full text text terms in full text text terms in full text Substances and their Chemical structure Chemical spectra physicochemical properties 3 REAXYS DESIGN Chemistry as the organizing principle With experimental data from journal REAXYS IS BUILT articles and patents Physical Data Physical Data Spectra Spectra Bioactivity Data Bioactivity Data Natural Product Natural Product Reaxys CHEMISTRY AS THE ORGANIZING PRINCIPLE Physicochemical Chemical Structures Reaxys excerpts all relevant data Properties even from footnotes and text Chemical Syntheses Pharmacology STRUCTURED TO HELP YOU SEARCH OTHER DATABASES REAXYS CATALOGUED AND TAXONMISED BY CHEMISTS FOR CHEMISTS ESSENTIAL TITLES BIBLIOGRAPHIC APPROACH ACROSS TIME/LITERATURE UNFOCUSED RESULTS USE-CASE DRIVEN FURTHER SEARCH NEEDED RELEVANT ANSWERS 50,000,000 RESULTS RETURNED 7 REAXYS INCLUDES Patent Content: English language only patents from the major chemistry patent classes of the US, European, and World PatentLiteratureCoverage Offices Content: from 1771 16,000 - present periodicals We are adding Asian patents – ecpected completion 2016 REAXYS INCLUDES Over 500 million facts Over 400+ searchable data fields HIGH QUALITY experimental results KEYWORDS A single bibliographic record in Reaxys contains index keywords from: Authors, Compendex, Embase, Geobase, Medline and Reaxys. Our competition has keywords only from two sources: CAplus and Medline Searching for classes of substances in Reaxys Found in REAXYS SUBSTANCE RECORDS Found in KEYWORDS in REAXYS BIBLIOGRAPHIC … and … RECORDS CLASSIC ORGANICS POLYMERS ALLOYS & METALS ORGANOMETALLICS COORDINATION COMPOUNDS CERAMICS CLASSIC INORGANICS NUCLEIC ACIDS & PROTEINS Search Substances Context Search Literature Context 11 WHAT IS REAXYS 2015? CONTENT: MANY DATABASES ALL IN ONE A Bibliographic A Substance Database Database >48 million records > 78 million substances (from ~16,000 journal titles (total) plus records from key patent organisations) ~ 57 million substances (unique) Reaxys 2015 A Chemical A Property Reaction Database Database > 500 million experimental properties > 38 million single- and in > 400 fields multi-step reactions in > 130 subject areas 12 SEARCH • What are the search options? • Substances • Reactions • Literature SEARCH • Properties • Is there “search REAXYS: SIMPLER TO SEARCH, MORE DISCOVERABLE INFORMATION intelligence”? • Truncation • Proximity • Algorithmic interpretation of natural language query Perform a literature Ask Reaxys, a quick, search easy topic ‘concept search’ Open Reaction search form Browse database via taxonomies rather Data search than search form by “property” database Access detailed Biodata, Open a structure Search using and MedChem specific search form chemical identifiers features 13 SEARCH SUBSTANCES SEARCH STRUCTURE, NAME, OR FORMULA – IN FULL, OR IN PART SEARCH SUBSTANCES SEARCH STRUCTURE, NAME, OR FORMULA – IN FULL, OR IN PART ADD OR REMOVE SEARCH FIELDS SEARCH REACTIONS SEARCH BY STRUCTURE, DATA, OR TYPE STRUCTURE DATA TYPE Atom mapping Bond forming/breaking Search reactions by structure Search reactions by reaction Search reactions by type or conditions name ✔✔✔ ✔✔✔ ✔✔✔ 17 SEARCH LITERATURE OUR GOAL: MAKE CONTENT MORE DISCOVERABLE, MORE EASILY! Ask Reaxys Reaxys Tree You are in control Ask Reaxys provides new ReaxysTree lets users user experience for text “browse” the database by searching: content better taxonomies: helps with discoverable, answers more search precision and answer You can also search with immediately available comprehension truncation/proximity – like you do through other interfaces Intelligent interpretation of Browse through taxonomies Use truncation/proximity if topic query you like ✔✔✔ ✔✔✔ ✔✔✔ 18 | 19 MAKE A COMPOUND 20 SYNTHESIS PLAN: AUTOMATES THE UNDERLYING PROCESSES IN CREATING SYNTHESIS ROUTES 21 SHOW EXPERIMENTAL PROCEDURE 22 PRESENTER | DATE | NAME OF PRESENTATION TI02 - PROPERTIES 23 | 24 FIND: A polymer shape EXAMPLE: Comb shaped polyacrylates The various shapes of polymer backbones may easily be searched by words: 25 EXAMPLE: Mechanical Properties of FIND: Property of a Polymer Polytetrafluoroethylene General Mechanical Properties, or specific Mechanical Properties (such as Young’s modulus) may easily be found through searches in the CITATION BASIC INDEX QUERYLET. Simply type in the entry field, take note of the auto-suggest terms (and perhaps use them as a guide to application of truncation) 26 Back to ca. 1 minute fully meet expectations referring slide MOLECULAR FORMULA MOLECULAR FORMULA BUILDER 27 Chrome compounds 28 CHROME COMPOUNDS Find substances that contain Cr and C 29 CHROME COMPOUNDS All carbon + chromium- containing substances All “inorganic” chromium- containing substances All carbon + chromium- containing substances All chromium-containing substances 30 CHROME COMPOUNDS (Yellow Inorganics) > 900,000 YELLOW SUBSTANCES 31 CHROME COMPOUNDS (Yellow Inorganics) 32 CHROME COMPOUNDS (Yellow Inorganics) 33 borosilicate glass Power of lookup 34 ALLOYS USING THE ALLOY QUERY FORM INITIAL ALLOY SEARCH OPTIONS 35 PRESENTER | DATE | NAME OF PRESENTATION ROTATE 3D VIEW 36 CHECK COMMERCIAL AVAILABILITY 37 SUPPORTS DIFFERENT STRUCTURE EDITORS 38 REPORTING: GATHER AND PREPARE THE INFORMATION 39 INTEROPERABILITY REAXYS MEDICINAL CHEMISTRY 41 WHY IS IT SO DIFFICULT TO MAKE DRUGS? Estimates of the number of possible drug molecules average 1040. In contrast, the number of seconds since the Big Bang is only 1017. If 10,000 chemists were to prepare 1 compound each per second, it would take 10,000,000,000,000,000,000,000,000,000 years to finish the job. ESSENTIAL INFORMATION: 100+ EXPERIMENTAL FIELDS Reaxys Medicinal Chemistry excerpts all the relevant Quantitative data 43 … BUT IT'S NOT THAT SIMPLE, MEDICINAL CHEMISTS FOR INSTANCE NEED TO COLLECT, ORGANIZE AND COMPARE INFORMATION FROM DIFFERENT SOURCES… THIS IS TIME CONSUMING AND ERROR PRONE ? ? ? ? 44 … BUT IT'S NOT THAT SIMPLE, MEDICINAL CHEMISTS FOR INSTANCE NEED TO COLLECT, ORGANIZE AND COMPARE INFORMATION FROM DIFFERENT SOURCES… THIS IS TIME CONSUMING AND ERROR PRONE 45 AND TO MAKE A DECISION ON WHICH EXPERIMENT TO DO, YOU WANT TO ORGANIZE YOUR CONTENT, NORMALIZE AND COMPARE, TO UNDERSTAND WHICH COMPOUND INTERACTS WITH WHICH TARGET AND TRIGGER WHICH BIOLOGICAL EFFECT—THAT'S A LOT OF MANUAL WORK! 46 RESULTS VIEW - HEATMAP Manage X and Y axis Bioactivity data based on pX values 47 48 EXAMPLE: SUBSTANCES ACTIVE ON COX-2 49 EXAMPLE: SUBSTANCES ACTIVE ON COX-2 50 EXAMPLE: AND NOT ACTIVE ON COX-1 51 EXAMPLE: AND NOT ACTIVE ON COX-1 EXAMPLE: AND NOT ACTIVE ON COX-1 EXAMPLE: SUBSTANCES ACTIVE SELECTIVELY ON COX-1 AND COX-2 ANTAGONIST WITH LOW ACTIVITY ON 5-HYDROXYTRYPTAMINE RECEPTOR ANTAGONIST WITH LOW ACTIVITY ON 5-HYDROXYTRYPTAMINE RECEPTOR ANTAGONIST WITH LOW ACTIVITY ON 5-HYDROXYTRYPTAMINE RECEPTOR RMC 2 CONTENT Patents Origin and starting date « The most comprehensive medicinal chemistry solution on the market » >90 000 Patents • US : 1971-present • EP : 1979-present • WO : 1978-present (English only) • Patents are coming from the A61K class mainly but not only. Articles and Journals • >5000 Journals Covered • >230 000 Articles • From 1980 to Present Drugable Targets • >9000 Drugable Targets 58 EXPORT CAPABILITIES 59 RMC2 EXPORT AND OUTPUT CAPABILITIES Export Import SD file RMC2 Export format includes : - XML, Excel, SD file RMC2 Export includes : - Substances and Physchem properties - Bioactivities and Bioassays - Targets - Bibliographic references RMC2 Export is compatible with : - Pipeline pilot 60 - Spotfire Etc… RMC2 EXCEL EXPORT AND SCATTER PLOT GENERATION No additional data TARGET SELECTIVITY improvement is need for Excel Scatterplot Performed Scatter plot Export For selectivity • Search for Substances tested on COX-1 and Cox-2 <20 minutes 12 COX2 versus COX1 Selectivity Based on pX COX 2 Selective compounds COX2 Selective compounds pX on COX >7 and pX on10 COX1 <6 at least a 10 fold Selectivity index 8 6 pX COX2 pX 4 2 pX COX1 61 0 0 1 2 3 4 5 6 7 8 9 10 PIOTR GOLKIEWICZ LIFE SCIENCES SOLUTION CONSULTANT CENTRAL EASTERN EUROPE [email protected] MOBILE: +48 695 30 60 17 62 .