High-Throughput Pharmacokinetics for Drug Discovery

Authors: Clark RD, Daga PR, Fraczkiewicz R
Conference: QSAR
Keywords: ADMET, CYP, P450, pKa, QSAR, solubility
Software: ADMET Predictor®, GastroPlus®
Division: Simulations Plus

Outline

  • Many Key Properties Can be Estimated Individually in silico
  • Acid/base dissociation constants (pKa ’s) & ionization
  • Solubility and tendency to supersaturate
  • Lipophilicity
  • Intestinal permeability
    • quantitative: passive permeability & local models
    • qualitative: susceptibility to active uptake or efflux on transporters
  • Metabolism
    • quantitative: cytochrome P450 (CYP) clearance & local models
    • qualitative: glucuronidation & glutathione conjugation
  • Binding to plasma proteins, to red blood cells & within tissues

18th International Conference on QSAR in Environmental and Health Sciences, June 11-15, 2018, Bled, Slovenia

By Robert D. Clark, Pankaj R. Daga and Robert Fraczkiewicz