2007 AAPS Annual Meeting and Exposition
November 11–15, 2007
San Diego Convention Center
San Diego, CA, USA
Conference Details
Booth # 2700
Poster Details
Monday, November 12th
Exhibit Hall: 1:00–5:00 PM
Poster #: M1088
The Rule of Five Revisited—Applying LogD in Place of LogP in Drug-Likeness Filters
Sanjivanjit K. Bhal, Karim Kassam, Ian G. Peirson, and Greg M. Pearl
Abstract: The much publicized "Rule of 5" (Ro5) has been widely adopted in the pharmaceutical industry as the first step in the virtual screening of compound libraries, in an effort to eliminate hits that are deemed to have poor physicochemical properties for oral bioavailability.
LogP is a key parameter in the Ro5 and although useful, it fails to take into account variation in drug lipophilicity due to ionization under physiological conditions. Given that >95% of commercial pharmaceuticals contain an ionizable moiety, we proposed that logD should be used as an alternate descriptor for lipophilicity in the Ro5, to reduce the number of potential false-positives eliminated in screening.
To this end, an adapted Ro5 was applied to a series of commercial compound libraries, applying logD in place of logP. Notable improvements in pass rate for compounds with desired lipophilicity (at pH 5.5) were observed, indicating that logD should be used preferentially over logP in drug-likeness filters.
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