ACS reports that recent paper is one of the 10 most accessed articles on the publication website.
Toronto, ON, Canada (February 27, 2008)—A paper published in Molecular Pharmaceutics in 2007 is now one of the journal’s 10 most accessed articles, according to the journal website’s rankings. The study, written by researchers at Advanced Chemistry Development, Inc., (ACD/Labs) examines the suitability and advantages of applying the molecular property, logD, in place of logP when filtering compound libraries for drug-likeness.
The ‘Rule-of-5’, generally considered a good starting point in determining whether a compound is likely to be a suitable drug candidate for oral administration, places significant emphasis on logP. This is a measure of lipophilicity and is related to the ability of a compound to permeate a lipid barrier such as the human cell membrane. LogP, however, measures lipophilicity of the neutral molecule (a rare state for >90% of drugs currently on the market), while logD represents lipophilicity of a molecule at any given pH—a more realistic approach considering the variety of pH environments a drug molecule encounters on its path through the body.
Researchers at Pfizer originally published findings that the likelihood of a drug candidate having acceptable permeability and solubility in a biological system could be estimated by comparing its characteristics against a set of parameters including molecular weight, number of proton donors, number of N and O atoms, and ClogP. The set of rules, now commonly referred to as Lipinski’s Rule-of-5, appeared in a paper entitled ‘Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings’ (Adv. Drug Delivery Rev., 23(1–3): 3–25, 1997).
Many scientists involved in pharmaceutical research have tweaked these rules over the last decade. This new publication, however, questions the legitimacy of applying the overly-simplified parameter, logP, in light of the availability of tools to quickly predict and apply logD. Application of the latter, more realistic property is shown to reduce the elimination of drug-like molecules and potentially viable drugs, and implies that larger assortments of compounds could form the basis of drug discovery projects. This could translate into less wasted efforts and more focused approaches for new pharmaceuticals.
The ACD/Labs study, ‘The Rule of Five Revisited-Applying LogD in Place of LogP in Drug-Likeness Filters’ (J. Mol. Pharm., 4: 556–560, 2007) was also presented as a poster at the 2007 AAPS National Meeting in San Diego, California.
For more information about the difference between logP and logD visit our website.
About Advanced Chemistry Development
Advanced Chemistry Development, Inc., (ACD/Labs) creates innovative software packages that aid chemical research scientists worldwide with spectroscopic validation of structures, elucidation of unknown substances, chromatographic separation, medicinal chemistry, preformulation of novel drug agents, systematic nomenclature generation, and chemical patenting and publication. Founded in 1994, and headquartered in Toronto, Canada, ACD/Labs employs a team of over 145 dedicated individuals whose continual efforts carry ACD/Labs’ innovative technologies into pharmaceutical, biotech, chemical, and materials companies throughout the world. Information about Advanced Chemistry Development and its products is available at www.acdlabs.com