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Talk: G-Protein coupled receptors in drug discovery (42 min)

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X Navigable Slide Index
  1. Introduction
  2. Protein family size: a significant opportunity
  3. GPCRs as drug targets
  4. It's a GPCR world?
  5. A GPCR world? - 2012 FDA approvals
  6. Why a reduction in GPCR drugs?
  7. AstraZeneca target screening success
  8. GPCRs have liabilities associated with them
  9. Have we picked all the low hanging fruit?
  10. GPCRs continuing to shape drug discovery
  11. There remain 140 nonolfactory orphan GPCRs
  12. New screening and pairing publications
  13. New technologies
  14. Commercially available screening technologies
  15. 120 years of research
  16. Now there are many different GPCR structures
  17. Examples of fragment based screening
  18. Companies that targets GCPRs
  19. Understanding of ligand receptor binding sites
  20. Facilitating allosteric modulator approaches
  21. Multiple binding pockets in family A receptors
  22. Intracellular binding pockets in family A
  23. Example of intracellular allosteric binding site
  24. How can we exploit these for drug discovery?
  25. Impact: marketed products and company focus
  26. We are also learning about GPCR signaling
  27. How the GPCR diagram looks today
  28. Ligand biased signaling
  29. Compounds in G-protein and beta-arrestin paths
  30. Dynamic mass redistribution and pathway assays
  31. Splice variants can modulate coupling
  32. Better drugs based on ligand bias knowledge
  33. Example for a drug based on ligand bias
  34. Opportunities for new drugs at validated targets
  35. Combining allosterism with ligand bias (1)
  36. 6 ligands with different signaling properties
  37. BETP a positive modulator of oxyntomodulin?
  38. BETP negative allosteric modulator of GLP-1?
  39. Combining allosterism with ligand bias (2)
  40. A simple picture can become complicated
  41. Acknowledgements
  42. END
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DETAILED SLIDE INDEX

  1. 1. Introduction
  2. 2. Protein family size: a significant opportunity
  3. 3. GPCRs as drug targets
  4. 4. It's a GPCR world?
  5. 5. A GPCR world? - 2012 FDA approvals
  6. 6. Why a reduction in GPCR drugs?
  7. 7. AstraZeneca target screening success
  8. 8. GPCRs have liabilities associated with them
  9. 9. Have we picked all the low hanging fruit?
  10. 10. GPCRs continuing to shape drug discovery
  11. 11. There remain 140 nonolfactory orphan GPCRs
  12. 12. New screening and pairing publications
  13. 13. New technologies
  14. 14. Commercially available screening technologies
  15. 15. 120 years of research
  16. 16. Now there are many different GPCR structures
  17. 17. Examples of fragment based screening
  18. 18. Companies that targets GCPRs
  19. 19. Understanding of ligand receptor binding sites
  20. 20. Facilitating allosteric modulator approaches
  21. 21. Multiple binding pockets in family A receptors
  22. 22. Intracellular binding pockets in family A
  23. 23. Example of intracellular allosteric binding site
  24. 24. How can we exploit these for drug discovery?
  25. 25. Impact: marketed products and company focus
  26. 26. We are also learning about GPCR signaling
  27. 27. How the GPCR diagram looks today
  28. 28. Ligand biased signaling
  29. 29. Compounds in G-protein and beta-arrestin paths
  30. 30. Dynamic mass redistribution and pathway assays
  31. 31. Splice variants can modulate coupling
  32. 32. Better drugs based on ligand bias knowledge
  33. 33. Example for a drug based on ligand bias
  34. 34. Opportunities for new drugs at validated targets
  35. 35. Combining allosterism with ligand bias (1)
  36. 36. 6 ligands with different signaling properties
  37. 37. BETP a positive modulator of oxyntomodulin?
  38. 38. BETP negative allosteric modulator of GLP-1?
  39. 39. Combining allosterism with ligand bias (2)
  40. 40. A simple picture can become complicated
  41. 41. Acknowledgements
  42. 42. END

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TALK'S CITATION

Wigglesworth, M. (2014), "G-Protein coupled receptors in drug discovery", in Arkin, M.R. (ed.), Small Molecule Drug Discovery: , The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL1683658)

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ABOUT THIS TALK

Speaker(s)

Dr. Mark Wigglesworth Show Biography

SPEAKER BIOGRAPHY

Dr. Mark Wigglesworth – AstraZeneca, UK

Mark Wigglesworth joined AstraZeneca in Sept 2012 to lead the newly formed Global High Throughput Screening Centre. His screening experience was gained at SmithKline Beecham and then GlaxoSmithKline where he worked extensively in GPCR drug discovery initiating and leading a number of projects to deliver lead molecules to drug discovery programmes. Mark has led groups of scientists responsible for delivery of structure activity relationship data to iterative chemistry programmes as well as working within Compound Management. Mark has contributed to numerous publications in the field of GPCR pharmacology and Compound Management including editing a book describing the Management of Biological and Chemical Samples for Screening Applications. In his current role he leads a team of more than 20 scientists dedicated to identifying novel chemical starting points for drug discovery programmes.

Publication Date

February, 2014

Topics Covered

The G-protein coupled receptor superfamily... more

TOPICS COVERED IN THIS TALK

  • The G-protein coupled receptor superfamily
  • GPCRs as drug targets
  • Approved GPCR drugs
  • why the reduction in GPCR drugs
  • new screening technologies and new drug targets

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