• An Overview of Drug Discovery and Development
• 78 min
  1. Rules and filters and their impact on success in chemical biology and drug discovery

  • Dr. Christopher Lipinski
• 37 min
  2. Where did drugs come from?

  • Dr. David Swinney
• Target Selection in Early Stage Drug Discovery
• 42 min
  3. G-Protein coupled receptors in drug discovery

  • Dr. Mark Wigglesworth
• 42 min
  4. Enzymology in drug discovery 1

  • Prof. Robert Copeland
• 66 min
  5. Enzymology in drug discovery 2

  • Prof. Robert Copeland
• 41 min
  6. Inhibiting protein-protein interactions 1

  • Dr. Adrian Whitty
• 35 min
  7. Inhibiting protein-protein interactions 2

  • Dr. Adrian Whitty
• Key Drug Discovery Challenges in Major Therapeutic Areas
• 64 min
  8. Current trends in antiviral drug development

  • Prof. Dr. Erik De Clercq
• 27 min
  9. The challenge of developing drugs for neglected parasitic diseases

  • Prof. James Mckerrow
• 55 min
  10. Is there a role for academia in drug discovery

  • Dr. Adrian J. Ivinson
• 31 min
  11. Key drug discovery challenges in cardiovascular medicine

  • Dr. Dan Swerdlow
  • Dr. Michael V. Holmes
• Methods of Hit Identification
• 46 min
  12. Fragment-based lead discovery

  • Dr. Daniel A. Erlanson
• Medicinal Chemistry and SAR
• 53 min
  13. Hit to lead

  • Dr. Michael Rafferty
• 37 min
  14. Prodrug strategies to overcome problems in drug therapy

  • Prof. Jarkko Rautio
• 40 min
  15. Deep ocean microorganisms yield mechanistically-novel anticancer agents

  • Prof. William Fenical
• From Lead to Drug
• 25 min
  16. Biomarkers in drug development: potential use and challenges

  • Dr. Abdel-Bassett Halim
• Case Studies in Drug Discovery
• 35 min
  17. Current concepts for the management of patients with osteoporosis

  • Dr. Michael Lewiecki
• 35 min
  18. Discovery of Levetiracetam (Keppra(R)): The first SV2A ligand for the treatment of epilepsy

  • Dr. Henrik Klitgaard
• 36 min
  19. Teixobactin kills pathogens without detectable resistance

  • Prof. Kim Lewis
• 20 min
  20. Discovery of schizophrenia drug targets from DISC1 mechanisms

  • Prof. Atsushi Kamiya
• Archived Lectures *These may not cover the latest advances in the field
• 46 min
  21. CNS-drug design

  • Prof. Quentin Smith
• 38 min
  22. Imatinib as a paradigm of targeted cancer therapies

  • Prof. Brian Druker
• 44 min
  23. New and emerging treatments for osteoporosis

  • Dr. Michael Lewiecki
• 38 min
  24. Prodrugs and drug delivery

  • Prof. Jarkko Rautio

Printable Handouts

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Navigable Slide Index

1. Introduction
2. Outline of presentation
3. Central nervous system diseases
4. Drug market for CNS disorders
5. Traditional CNS drug targets
6. Novel CNS drug targets
7. Multiple obstacles for drug delivery to CNS
8. Pathways for drug exchange within the CNS
9. Factors affecting brain drug delivery and exchange
10. The structure of brain capillaries impedes uptake
11. Measures of drug uptake and distribution in brain
12. BBB permeability and solute lipid solubility
13. Tissues capillary PS and 95% equilibration time
14. Cerebral blood flow affects drug uptake and Kin
15. Initial uptake vs. steady-state distribution
16. Plasma protein binding and brain drug uptake
17. Example of the impact of plasma protein binding
18. Brain capillary drug transporters
19. Transporters and drug distribution across BBB
20. "Enzymatic" blood-brain barrier
21. Drug distribution in brain at steady state
22. Relation between bound and free drug
23. Free drug distribution ratio at steady state
24. BBB changes in pathology and disease
25. Drug-like properties to cross the BBB
26. Early findings in BBB drug uptake
27. Measures of lipophilicity
28. Passive permeability across lipid membranes
29. Drug ionization
30. Influence of pH on neutral fraction
31. Lipinski "rule of five"
32. "Rule of five" modified for CNS drugs
33. Impact of hydrogen bonds and alkyl groups
34. Examples of positive CNS drugs
35. Example of a poor CNS drug
36. Other in vitro measures
37. In vivo measures
38. Methods to improve brain uptake
39. Simple rules for efflux transporters
40. % drug distribution to brain
41. Biologic compounds
42. Closing comments of brain pharmacokinetics
43. Summary
44. Acknowledgements

Topics Covered

• Central nervous system diseases
• Drug market for CNS disorders
• Traditional CNS drug targets
• Novel CNS drug targets
• Multiple obstacles for drug delivery to CNS
• Pathways for drug exchange within the CNS
• The structure of brain capillaries impedes uptake
• Measures of drug uptake and distribution in brain
• BBB permeability and solute lipid solubility
• Tissues capillary PS and 95% equilibration time
• Cerebral blood flow affects drug uptake and Kin
• Initial uptake vs. steady-state distribution
• Plasma protein binding and brain drug uptake
• Brain capillary drug transporters
• Transporters and drug distribution across BBB
• "Enzymatic" blood-brain barrier
• Relation between bound and free drug
• Free drug distribution ratio at steady state
• BBB changes in pathology and disease
• Drug-like properties to cross the BBB
• Early findings in BBB drug uptake
• Measures of lipophilicity
• Passive permeability across lipid membranes
• Drug ionization
• Influence of pH on neutral fraction
• Lipinski "rule of five"
• Impact of hydrogen bonds and alkyl groups
• Positive CNS drugs
• Poor CNS drug
• in vitro measures
• In vivo measures
• Methods to improve brain uptake
• Simple rules for efflux transporters
• % drug distribution to brain
• Biologic compounds
• Brain pharmacokinetics

Links

Series:

• The Blood-Brain Barrier
• Small Molecule Drug Discovery

Categories:

• Neuroscience
• Pharmaceutical Sciences

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on March 1, 2008
• Archived on May 31, 2018

Financial Disclosures

• Prof. Quentin Smith has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.