Quality guidelines for oral drug candidates: dose, solubility and lipophilicity

• Published in: Drug discovery today 2016-10, Vol.21 (10), p.1719-1727
• Main Authors: Bayliss, Martin K., Butler, James, Feldman, Paul L., Green, Darren V.S., Leeson, Paul D., Palovich, Michael R., Taylor, Anthony J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Drug Discovery; Humans; Hydrophobic and Hydrophilic Interactions; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - metabolism; Solubility
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2016.07.007

[Display omitted] •Experimental properties of GSK's oral portfolio were compared with marketed drugs.•Properties were dose, solubility and the property forecast index (chromatographic Log D + aromatic ring count).•A model combining property cutoffs differentiated GSK's candidates from oral drugs.•The model provides guidance for seeking and selecting oral clinical candidates. In an attempt to seek increased understanding of compound attributes that influence successful drug pipeline progression, GlaxoSmithKline's portfolio of oral candidates was compared with reference sets of marketed oral drugs. The approach differs from other attrition studies by explicitly focusing on choosing ‘the right compound’ by applying relevant, experimentally derived properties. The analysis led to four proposed compound quality categories, created by combining specific criteria for three measures: dose, solubility and the property forecast index, a composite measure of lipophilicity using chromatographically determined LogD and aromaticity. The ‘three properties’ provide benchmarked guidelines for project teams to use when seeking and selecting clinical candidates, because they reflect the property distribution of marketed oral drugs.