Bioinformatics in drug discove

2. FBW 15-12-2011 Wim Van Criekinge

7. Example: Agro Known “lethal” genes from worm, drosphila Sequence Genome Filter for drugability”, tractibility & novelty

8. Example: Extremophiles Known lipases Filter for “workable”lipases at 90 º C Sequence Genome Functional Foods Convert Highly Energetic Monosaccharides to Dextrane Look for species with interesting phenotypes Clone and produce in large quantities Washing Powder additives

10. Drug Discovery: Design new drugs by computer ? Problem: pipeline cost rise linear, NCE steady Money: bypassing difficult, work on attrition Every step requires specific computational tools

20. “ Optimal” drug target Predict side effect Where is optimal drug target ? How to correct disease state Side effects ?

27. G enome-wide RNA i RNAI vector bacteria producing ds RNA for each of the 20.000 genes proprietary nematode responding to RNA i 20.000 responses 20.000 genes insert library

30. Normal insulin signaling Reduced insulin signaling fat storage LOW fat storage HIGH Type-II Diabetes

32. Pharma is conservative

34. Molecular functions of 26 383 human genes Structural Genomics

36. Lipinsky for the target ? Database of all “drugable” human genes

37. Drug Discovery: Design new drugs by computer ?

38. screening - the automated examination and testing of libraries of synthetic and/or organic compounds and extracts to identify potential drug leads, based on the compound's binding affinity for a target molecule. screening library - a large collection of compounds with different chemical properties or shapes, generated either by combinatorial chemistry or some other process or by collecting samples with interesting biological properties. High Throughput Screening : Quick and Dirty… from 5000 compounds per day Drug Discovery: Screening definitions

40. Drug Discovery: HTS – The Wet Lab Roboti c arm Read-out Fluorescence / luminescence D istribution 96 / 384 wells Optical Bank for stability

42. Drug Discovery HIT LEAD

48. Drug-like-ness (Celebrex) Methyl in this position makes it a weaker cox-2 inhibitor, but site of metabolic oxidation and ensures an acceptable clearance

49. To assist combinatorial chemistry, buy specific compunds

56. Drug Discovery Toxigenomics Metabogenomics

61. Drug Discovery & Development: IND filing

62. Hapmap

63. Pharmacogenomics Predictive/preventive – systems biology

64. Sneak preview Bioinformatics (re)loaded