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Issue 3, 2013
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Escape from Flatland 2: complexity and promiscuity

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Abstract

Toxicity plays a major role in attrition in the clinic and promiscuity has been linked to toxicity. A number of molecular descriptors have been identified that contribute to promiscuity including ionization and logP. In this study we report on the relationship between complexity, as measured by two descriptors [fraction sp3 (Fsp3) where Fsp3 = (number of sp3 hybridized carbons/total carbon count) and chiral carbon count], and promiscuity as well as Cyp450 inhibition. We find that increasing complexity reduces promiscuity and Cyp450 inhibition. As an understanding of key property descriptors has helped the pharmaceutical industry to address some of the deficiencies of compounds as pertains to bioavailability, awareness of the descriptors that impact promiscuity should allow us to better address toxicity in the clinic.

Graphical abstract: Escape from Flatland 2: complexity and promiscuity

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Publication details

The article was received on 19 Nov 2012, accepted on 13 Dec 2012 and first published on 19 Dec 2012


Article type: Concise Article
DOI: 10.1039/C2MD20347B
Citation: Med. Chem. Commun., 2013,4, 515-519
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    Escape from Flatland 2: complexity and promiscuity

    F. Lovering, Med. Chem. Commun., 2013, 4, 515
    DOI: 10.1039/C2MD20347B

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