Deuterated drugs in PubChem

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Presentation at BioIT World, Hannover, October 2010

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  • 5:1 tested untested
  • CID: 446157 72 assays inc ChEMBL (E,3R,5S)-7-[4-( CID: 6239562 56 assays mainly NCCG (E)-7-[4-(4 Three were esters eg tert-Butyl rosuvastatin; AC-3415; CID11478210
  • Rank by Mw 6 have same Mw 481 Three were esters eg tert-Butyl rosuvastatin; AC-3415; CID11478210
  • Same Connectivity cannonical smiles or core layer InChI CID date 2009-05-08 TP Deposit Date: 2009-05-04 DG Deposit Date: 2009-08-04 Other Ids 6 have same Mw 481 Three were esters eg tert-Butyl rosuvastatin; AC-3415; CID11478210
  • 6 have same Mw 481 Three were esters eg tert-Butyl rosuvastatin; AC-3415; CID11478210
  • Same Connectivity cannonical smiles or core layer InChI CID date 2009-05-08 TP Deposit Date: 2009-05-04 DG Deposit Date: 2009-08-04 Other Ids 6 have same Mw 481 Three were esters eg tert-Butyl rosuvastatin; AC-3415; CID11478210
  • Rank by Mw 6 have same Mw 481 Three were esters eg tert-Butyl rosuvastatin; AC-3415; CID11478210
  • Deuterogate Wiki Drugs Crowdsourcing
  • Deuterogate Wiki Drugs Crowdsourcing
  • Deuterogate Wiki Drugs Crowdsourcing
  • Deuterated drugs in PubChem

    1. 1. The Unforseen Consequences of Opportunistic Deuterated Drug Claims, Patent Extraction Feeds and the PubChem Chemistry Rules When data integration gets fuzzy Chris Southan ChrisDS Consulting, Göteborg, Sweden BioIT World, Hannover, Oct 2010
    2. 2. Background <ul><ul><li>The scale of chemistry-biology-bioinformatics connectivity has made PubChem a de facto global data integration hub. </li></ul></ul><ul><ul><li>However the fidelity of this is compromised by factors including : </li></ul></ul><ul><ul><li>Inherent complexities of chemical structure representation </li></ul></ul><ul><ul><li>Chemistry rules that, while rigourous, tend to split CIDs </li></ul></ul><ul><ul><li>Submitter primacy and a low proliferation bar </li></ul></ul><ul><ul><li>Vendor dilution of bioanotated with no-data compounds </li></ul></ul><ul><ul><li>Increasingly complex BioAssay relationships </li></ul></ul><ul><ul><li>Patent-extraction feeds from commercial sources </li></ul></ul>
    3. 3. Discordance of Drug Collections
    4. 4. Will the real Rosuvastatin stand up ?
    5. 5. But 15 CIDs ?
    6. 6. “ Heavy” Rosuvastatin (+28) CID 25241235
    7. 7. Patent Filings on Deuterated Drugs “ Protia's patents appear to be a blunderbuss approach, with a mass of US filings 237 published to date but only 11 PCT applications. None of these provide exemplification or any biological description. Concert has 39 PCTs and 26 US applications published, Auspex 57 PCTS and 39 US applications” (Comment from “In the Pipeline” blog, June 2009)
    8. 8. A Pipeline With Unintended Consequences
    9. 9. Some of them Might Just Work ? But we don’t know which one of the 25 !
    10. 10. Picking Off the Best-sellers Connectivity Deuteros 1) 38 32 2) 4 88 0 85 3) 15 12 7) 7 4 8) 8 7 9) 11 9 10) 68 66 13) 29 26 14 ) 51 48 15) 16 11
    11. 11. Sorting
    12. 12. Extent of the Problem
    13. 13. Does this Matter ? <ul><ul><li>In the grand scheme of things maybe not - but ........ </li></ul></ul><ul><ul><li>Not just the deuteros but other patent-extracted compounds , are causing CID ”multiplexing ” in PubChem (and ChemSpider) </li></ul></ul><ul><ul><li>The Pharma ”Crown-jewels” of marketed drugs are badly hit </li></ul></ul><ul><ul><li>Less experienced PubChem users could be confused </li></ul></ul><ul><ul><li>Some types of search results get messed up </li></ul></ul><ul><ul><li>They ”gum up” company internal integrated systems </li></ul></ul><ul><ul><li>Do we want prophetic or virtual structures in PubChem ? </li></ul></ul>
    14. 14. Solutions ? <ul><ul><li>On an individual basis you can sort drug CIDs by Mr as described </li></ul></ul><ul><ul><li>However, no filters can cleanly discriminate between data-supported or prophetic chemistry published in patents (i.e. the authentic wheat from the spurious chaff) </li></ul></ul><ul><ul><li>Patent-only flags on CIDs would be useful but as a filter they would remove many useful non-deuterateds </li></ul></ul><ul><ul><li>Filtering all Isotopically labeled compounds removes valuable experimental tools that are “in pots” </li></ul></ul><ul><ul><li>A (tiny?) fraction of the deuterated drugs may get data links </li></ul></ul><ul><ul><li>Drug crowdsourcing is already happening (e.g. Wikipedia) but we need the set to be flagged in PubChem </li></ul></ul><ul><ul><li>Some kind of “canonical clustering” in PubChem could help </li></ul></ul>
    15. 15. Questions ?

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