Datum der Aufzeichnung: 10 September 2014

Duration: 46 minutes 59 seconds

Isothermal Titration Calorimetry (ITC) is a label free technique for measuring the affinity, stoichiometry and thermodynamics of an interaction. It requires minimal sample preparation and delivers high quality affinity data in a fast, unattended experiment. The high quality of the data and the ease of use of the instrument has resulted in a wide spread adoption of the technique in early drug discovery programs. This presentation includes a number of examples where ITC has been used in hit validation, lead optimization and mechanism of action studies as well as a protein quality monitor in assay development laboratories.

Table of contents
1. From hit to lead - accelerate early drug discovery with ITC
02:16
2. MicroCal iTC200 and MicroCal Auto-iTC200
00:40
3. Why Microcalorimetry?
01:21
4. All binding parameters in a single experiment
01:36
5. Microcalorimetry provides a total picture of binding energetics
02:02
6. Same affinity, different energetics
02:18
7. With ITC you can…
01:42
8. Protein quality/assay development
01:27
9. ITC applications in drug discovery
00:25
10. MicroCal Auto-iTC200 in hit validation
00:28
11. Confirm binding-compare to IC50
00:40
12. Confirm binding-false positives
00:42
13. MicroCal ITC systems confirm 1 to 1 binding to active site
01:19
14. Hit validation of fragment screen against Vsp34: A drug discovery program to reduce resistance to cancer drugsCollaborative work between Sprint Biosciences and MicroCal Products
00:26
15. Overview
01:55
16. Vps34 Fragment-based screening: quality in focus
01:20
17. 85% of validated ligands gave co-crystal structures
00:45
18. Summary – ITC for hit validation
00:36
19. MicroCal Auto-iTC200 in MOA
00:13
20. Revealing kinase inhibitors mechanisms: ITC leads the wayApplication note Geoff Holdgate
00:13
21. MOA: ATP competitive binding
01:40
22. MOA: ATP uncompetitive binding
00:35
23. Inhibitor binding to the homodimer Caspase-3
01:11
24. Summary - ITC for MoA studies
00:23
25. MicroCal Auto-iTC200 in lead optimization
00:49
26. SAR by ITC
01:33
27. Support structure based lead optimization programs
00:31
28. Optimizing diaminopyrimidine renin inhibitors aided by ITC and structural data Abstracted from Ron Sarver, Current Trends in Microcalorimetry
00:08
29. The binding orientation of lead compound from high throughput screening
00:50
30. Data suggests substituting aryl-benzamide with aryl-sulfonamide to improve H-bonds
02:32
31. Renin inhibitor affinity improved 45X from initial 3.6 μM lead to 79nM
01:17
32. The best drugs have more enthalpic binding
01:55
33. Summary - ITC in lead optimization
00:49
34. Summary
01:24
35. Thank You!
07:25
36. Contact Information
01:33