Phenotypic Screens, Chemical Genomics, and Antimalarial Lead Discovery
2011

Antimalarial Lead Discovery and Chemical Genomics

publication Evidence: moderate

Author Information

Author(s): Garcia-Bustos Jose F., Gamo Francisco-Javier

Primary Institution: Tres Cantos Medicine Development Campus, GlaxoSmithKline, Spain

Hypothesis

What is the nature of the bias in chemical diversity identified in screens for Plasmodium falciparum?

Conclusion

The study suggests that a one-to-one correlation between chemical families and individual targets cannot be reliably established.

Supporting Evidence

  • Thousands of hit structures for Plasmodium falciparum are now publicly available.
  • The chemical diversity identified may not represent the necessary chemotypes to inhibit drugable targets.
  • Compounds in the same chemical family can show different effects on parasites.

Takeaway

Scientists are trying to find new medicines for malaria by looking at many different chemicals, but it's hard to know which ones will work because they can affect the germs in different ways.

Methodology

The study discusses the analysis of chemical screens against Plasmodium falciparum and the challenges in correlating chemical families with drug targets.

Potential Biases

The starting compound libraries are biased towards certain physicochemical properties and human targets.

Limitations

The study acknowledges the difficulty in estimating the coverage of target space and the subjective nature of chemical classification.

Digital Object Identifier (DOI)

10.1371/journal.ppat.1002156

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