title: Quality guidelines for oral drug candidates: dose, solubility and lipophilicity.
abstract: 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.
authors.affiliation: Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Electronic address: martin.k.bayliss@gsk.com.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Bayliss
authors.affiliation: GlaxoSmithKline R&D, Park Road, Ware, Hertfordshire SG12 0DP, UK.
authors.forename: James
authors.initials: J
authors.lastname: Butler
authors.affiliation: GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Feldman
authors.affiliation: Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Darren V S
authors.initials: DV
authors.lastname: Green
authors.affiliation: Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK; Paul Leeson Consulting Limited, The Malt House, Main Street, Congerstone, Nuneaton, Warks CV13 6LZ, UK. Electronic address: leesonpd@gmail.com.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Leeson
authors.affiliation: GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Palovich
authors.affiliation: Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Taylor
mesh_terms: D000284:Administration, Oral; D000818:Animals; D055808:Drug Discovery; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations