Friday, July 11, 2008

The rule of three and ADMET

Paul Gleeson from GSK has come up with a set of rules of thumb (DOI: 10.1021/jm701122q) for the three important property of drug namely molecular weight, log P and ionization state (which medicinal chemist comfortable and familiar with) that influence their ADMET behavior Such as Solubility, Permeability, Bioavailability, Volume of distribution, Plasma protein binding, CNS penetration, Brain tissue binding, P-gp efflux, hERG inhibition and Cytochrome - P450.
This study is important for pharmaceutical industry because in drug development up to 40 % of promising candidate failing in clinical trails due to unfavorable pharmacological properties.
His study re-emphasizes the need to focus on a lower molecular weight and log P area of physiochemical property space to obtain improved ADMET parameters.

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