4.7 Review

Can BDDCS illuminate targets in drug design?

Journal

DRUG DISCOVERY TODAY
Volume 24, Issue 12, Pages 2299-2306

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2019.09.021

Keywords

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Funding

  1. National Institutes of Health (NIH) Common Fund [U24CA224370, U24TR002278, U01CA239108]
  2. National Cancer Institute (NCI) [P3OCA118100]

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The fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we show that certain protein families have a clear preference for drugs with specific PK properties. We investigate this by cross-referencing 'druggable target' annotations for >1000 US Food and Drug Administration (FDA)-approved drugs with their PK profile, as defined by the Biopharmaceutics Drug Disposition Classification System (BDDCS) criteria, and then examine the BDDCS preference for several major target protein families and therapeutic categories. Our findings suggest a novel way to conduct drug discovery by focusing PK profiles at the very early stage of target selection.

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