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Open-Access Activity Prediction Tools for Natural Products. Case Study: hERG Blockers

  • Fabian Mayr
  • Christian Vieider
  • Veronika Temml
  • Hermann Stuppner
  • Daniela SchusterEmail author
Chapter
Part of the Progress in the Chemistry of Organic Natural Products book series (POGRCHEM, volume 110)

Abstract

Interference with the hERG potassium ion channel may cause cardiac arrhythmia and can even lead to death. Over the last few decades, several drugs, already on the market, and many more investigational drugs in various development stages, have had to be discontinued because of their hERG-associated toxicity. To recognize potential hERG activity in the early stages of drug development, a wide array of computational tools, based on different principles, such as 3D QSAR, 2D and 3D similarity, and machine learning, have been developed and are reviewed in this chapter. The various available prediction tools Similarity Ensemble Approach, SuperPred, SwissTargetPrediction, HitPick, admetSAR, PASSonline, Pred-hERG, and VirtualToxLab™ were used to screen a dataset of known hERG synthetic and natural product actives and inactives to quantify and compare their predictive power. This contribution will allow the reader to evaluate the suitability of these computational methods for their own related projects. There is an unmet need for natural product-specific prediction tools in this field.

Keywords

hERG Human ether-a-go-go-related gene Natural products Activity profiling Target prediction Virtual screening ADMET prediction 

Notes

Acknowledgments

The research has been funded by GECT Euregio Tirol-Südtirol-Trentino (IPN55). The authors thank OpenEye Scientific Software and Inte:Ligand for their academic licenses. Daniela Schuster is an Ingeborg Hochmair Professor at the University of Innsbruck.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Fabian Mayr
    • 1
    • 2
  • Christian Vieider
    • 2
  • Veronika Temml
    • 1
  • Hermann Stuppner
    • 1
  • Daniela Schuster
    • 2
    • 3
    Email author
  1. 1.Institute of Pharmacy/Pharmacognosy, University of InnsbruckInnsbruckAustria
  2. 2.Institute of Pharmacy/Pharmaceutical Chemistry, University of InnsbruckInnsbruckAustria
  3. 3.Department of Pharmaceutical and Medicinal ChemistryInstitute of Pharmacy, Paracelsus Medical University SalzburgSalzburgAustria

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