This page contains information and questions from the Chemical Screening session and the responses provided.
Major points from Peter Ertl's talk
2000 viable drug targets, many tens of thousands of possible drugs
- ‘Bioavailability area’ - small area of molecular property space
- Drug-likeness and NP-likeness
- ChemGPS - from AZ - molecules with “extreme properties ” used as reference
- http://chemgps.bmc.uu.se/batchelor/queue.php?show=submit
- So look for something similar
- Molecules produced by living organisms - primary metabolites (fatty acids, sugars…) and secondary metabolites (unique to an organism, antibiotics, marine toxins…)
- Long natural selection process to optimize bio-interaction
What about bioisosteres in Peter's classification system and their potential use?
- Analysis of bio-activity databases (ChEMBL) can provide many ideas for new bioisosteres
Isn’t the decision to use secondary metabolites and not primary metabolites arbitrary?
- This process is used early on in the project to find basic information
- Later on incorporate 3D structures and modelling
- Classification of bio-activity is still important
Do natural products have to be considered with regards to membrane transport?
- There are some known structural features for transporter proteins (mainly sugars transporters)
- These need to be thought about, but it isn't simple
- Ideally need to be considered for each new compound
Will we ever have an overlap between synthetic chemistry and natural products?
- Potentially yes
- Scope for developing non-natural, natural products
- Engineering natural products to create simpler compounds
Do you characterise cyto-toxic compounds when creating potential libraries and exclude them?
- Yes, a large set of sub-structures is excluded from screens due to these properties