PASS: identification of probable targets and mechanisms of toxicity

SAR QSAR Environ Res. 2007 Jan-Mar;18(1-2):101-10. doi: 10.1080/10629360601054032.

Abstract

Toxicity of chemical compound is a complex phenomenon that may be caused by its interaction with different targets in the organism. Two distinct types of toxicity can be broadly specified: the first one is caused by the strong compound's interaction with a single target (e.g. AChE inhibition); while the second one is caused by the moderate compound's interaction with many various targets. Computer program PASS predicts about 2500 kinds of biological activities based on the structural formula of chemical compounds. Prediction is based on the robust analysis of structure-activity relationships for about 60,000 biologically active compounds. Mean accuracy exceeds 90% in leave-one-out cross-validation. In addition to some kinds of adverse effects and specific toxicity (e.g. carcinogenicity, mutagenicity, etc.), PASS predicts approximately 2000 kinds of biological activities at the molecular level, that providing an estimated profile of compound's action in biological space. Such profiles can be used to recognize the most probable targets, interaction with which might be a reason of compound's toxicity. Applications of PASS predictions for analysis of probable targets and mechanisms of toxicity are discussed.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Barbiturates / chemistry
  • Barbiturates / toxicity
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / toxicity
  • Computer Simulation*
  • Drug-Related Side Effects and Adverse Reactions*
  • Isoquinolines / chemistry
  • Isoquinolines / toxicity
  • Molecular Structure
  • Pharmaceutical Preparations / chemistry*
  • Sarin / chemistry
  • Sarin / toxicity
  • Structure-Activity Relationship

Substances

  • Barbiturates
  • Cholinesterase Inhibitors
  • Isoquinolines
  • Pharmaceutical Preparations
  • Sarin
  • barbituric acid