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Pharma jargon: Lipinski’s rule of five

jargon: noun. Special words or expressions that are used by a particular profession or group and are difficult for others to understand. [g]

The point of this blog’s “pharma jargon” series is to highlight key words commonly encountered in drug discovery research.

Lipinski’s rule of five. This is a widely known set of guidelines for predicting how well a drug will perform when taken orally. Christopher Lipinski at Pfizer developed this principle in 1997, when he observed that most drugs taken via mouth are pretty small and pretty lipophilic. So this doesn’t so much focus on how well the drug binds, but more so on can the drug get there, i.e., absorption and permeability.

In generally, an orally active drug should fulfill these criteria:

  • 5 or fewer hydrogen bond donors
  • 10 or fewer hydrogen bond acceptors
  • 500 or lower molecular mass in daltons (500 Da = 500 g/mol)
  • 5 or less for octanol-water partition coefficient

These are rough set of guidelines, and there are many variants of it, but this is the general framework to keep in mind.

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