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Expert Opinion on Drug Discovery Volume 11, 2016 - Issue 2
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Reviews

Non-stoichiometric inhibition in integrated lead finding – a literature review

Martin KlumppNovartis Institute of Biomedical Research Basel, Novartis Pharma AG, Basel, SwitzerlandCorrespondence[email protected]
Pages 149-162 | Received 09 Oct 2015, Accepted 03 Dec 2015, Published online: 31 Dec 2015

References

  • Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
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• Easy-to-read, sometimes humorous and provocative, introduction to the topic.

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• Illustrates how the apparent potency of non-stoichiometric inhibitors shifts upon varying enzyme concentration

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•• Contains numerous examples of various counterscreens to eliminate different types of non-stoichiometric inhibitors.

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•• Analyzes the typical results measured in biophysical binding assays for stoichiometric and non-stoichiometric inhibitors. A valuable reference.

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• Demonstrates how the potency of a stoichiometric inhibitor is unaffected by enzyme concentration.

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• Outlines some pecularities of natural products that are critical when screening such samples.

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•• Suggests valuable novel approaches for state-of-the-art in silico hit list analysis.

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• A classic example of how assay artifacts can derail drug discovery.

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•• A prime example of how various approaches and techniques can be integrated into a meaningful flowchart for efficient lead finding.

• A good introduction to the concept of ‘target engagement’ and its role at various stages of the drug discovery pipeline.

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• Contains some interesting thoughts on how to apply target engagement assays.

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