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Scientific article
English

Predicting blood-brain barrier permeation from three-dimensional molecular structure

Published inJournal of medicinal chemistry, vol. 43, no. 11, p. 2204-2216
Publication date2000
Abstract

Predicting blood-brain barrier (BBB) permeation remains a challenge in drug design. Since it is impossible to determine experimentally the BBB partitioning of large numbers of preclinical candidates, alternative evaluation methods based on computerized models are desirable. The present study was conducted to demonstrate the value of descriptors derived from 3D molecular fields in estimating the BBB permeation of a large set of compounds and to produce a simple mathematical model suitable for external prediction. The method used (VolSurf) transforms 3D fields into descriptors and correlates them to the experimental permeation by a discriminant partial least squares procedure. The model obtained here correctly predicts more than 90% of the BBB permeation data. By quantifying the favorable and unfavorable contributions of physicochemical and structural properties, it also offers valuable insights for drug design, pharmacological profiling, and screening. The computational procedure is fully automated and quite fast. The method thus appears as a valuable new tool in virtual screening where selection or prioritization of candidates is required from large collections of compounds.

Keywords
  • Blood-Brain Barrier
  • Databases, Factual
  • Models, Chemical
  • Molecular Conformation
  • Multivariate Analysis
  • Permeability
  • Pharmaceutical Preparations/*chemistry
  • Pharmacokinetics
  • Structure-Activity Relationship
Affiliation Not a UNIGE publication
Citation (ISO format)
CRIVORI, P. et al. Predicting blood-brain barrier permeation from three-dimensional molecular structure. In: Journal of medicinal chemistry, 2000, vol. 43, n° 11, p. 2204–2216. doi: 10.1021/jm990968%2B
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ISSN of the journal0022-2623
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