title: Computational tools and resources for metabolism-related property predictions. 2. Application to prediction of half-life time in human liver microsomes.
abstract: BACKGROUND
  The most important factor affecting metabolic excretion of compounds from the body is their half-life time. This provides an indication of compound stability of, for example, drug molecules. We report on our efforts to develop QSAR models for metabolic stability of compounds, based on in vitro half-life assay data measured in human liver microsomes.
  
  
  METHODS
  A variety of QSAR models generated using different statistical methods and descriptor sets implemented in both open-source and commercial programs (KNIME, GUSAR and StarDrop) were analyzed. The models obtained were compared using four different external validation sets from public and commercial data sources, including two smaller sets of in vivo half-life data in humans.
  
  
  CONCLUSIONS
  In many cases, the accuracy of prediction achieved on one external test set did not correspond to the results achieved with another test set. The most predictive models were used for predicting the metabolic stability of compounds from the open NCI database, the results of which are publicly available on the NCI/CADD Group web server ( http://cactus.nci.nih.gov ).
authors.affiliation: CADD Group, Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Zakharov
authors.forename: Megan L
authors.initials: ML
authors.lastname: Peach
authors.forename: Markus
authors.initials: M
authors.lastname: Sitzmann
authors.forename: Igor V
authors.initials: IV
authors.lastname: Filippov
authors.forename: Heather J
authors.initials: HJ
authors.lastname: McCartney
authors.forename: Layton H
authors.initials: LH
authors.lastname: Smith
authors.forename: Angelo
authors.initials: A
authors.lastname: Pugliese
authors.forename: Marc C
authors.initials: MC
authors.lastname: Nicklaus
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D016208:Databases, Factual; D006207:Half-Life; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D004364:Pharmaceutical Preparations