Greater than the sum of the parts – issues in drug discovery

Inspired by the years of reading and also recent collaborative forays into the complexity of data quality and tools used for dispensing in HTS I have started to list issues that we need to be aware of in drug discovery (“anything that can go wrong – which will go wrong”).

1. How you move liquids matters – acoustic vs tips vs pins vs inket vs other methods

2. Plastics used in labware can leach and interfere with compounds / assays

3. Compounds can aggregate – continues to be a problem

4. Frequent hitters and promiscuous compounds in HTS screens

5. Solvents used in solubilizing

6. Detergent effects on assays / biological systems

7. Data reproducibility / e.g. target validation, inter-lab variability

8. Data quality, data access, structure quality/availability in patents and databases

9. False positives (reporter issues – luciferase), fluorescence

10. Data handling – edge effects, statistical analyses

11. Biases introduced by filtering libraries

12. Sparse coverage of chemical space in screening libraries vs target space vs physichemical property space

With all of the above to consider it is surprising that drug discovery is as productive as it is…oops maybe its because of these combined that it is so complex / difficult / near impossible to find new drugs.

Perhaps in future we could propose some solutions from which everyone can benefit. I welcome additions and suggestions, so please get in touch.



Leave a Reply

Your email address will not be published.

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>