title: ADME related profiling in 96 and 384 well plate format--a novel and robust HT-assay for the determination of lipophilicity and serum albumin binding.
abstract: The failure of about half of the drug candidates is associated with poor pharmacokinetic properties leading to a huge loss of time and money [1]. Early profiling of drug like properties provides important information in order to screen out insoluble, poorly absorbed and toxic compounds. Today, large compound libraries have to be screened, and of course the total number of compounds will rise over the next years leading to a growing demand for fully automated assays. A balance between quality, speed, throughput, cost and information content can be accomplished by the careful selection of assays and experimental conditions. Here we describe a novel 384 well format assay for two important ADME related descriptors (lipophilicity and serum protein binding) as input parameters for a precise prediction of fraction absorbed, blood/organ distribution coefficients and permeability, in order to maximize the information about a compound at an early stage of discovery.
authors.affiliation: Nimbus Biotechnologie Gmbh, Eilenburger Str 4, 04317 Leipzig, Germany. thorsten.lhartmann@numbus-biotech.com
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hartmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmitt
authors.forename: Cornelia
authors.initials: C
authors.lastname: Röhring
authors.forename: Daniel
authors.initials: D
authors.lastname: Nimptsch
authors.forename: Joachim
authors.initials: J
authors.lastname: Nöller
authors.forename: Christoph
authors.initials: C
authors.lastname: Mohr
mesh_terms: D002851:Chromatography, High Pressure Liquid; D008051:Lipid Bilayers; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism*; D012995:Solubility
chemical_list: D008051:Lipid Bilayers; D004364:Pharmaceutical Preparations; D012709:Serum Albumin