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De Novo Fragment Design for Drug Discovery and Chemical Biology.
Journal article

De Novo Fragment Design for Drug Discovery and Chemical Biology.

  • Rodrigues T Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Reker D Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Welin M SARomics Biostructures AB, Medicon Village, 22381 Lund (Sweden).
  • Caldera M Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Brunner C Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Gabernet G Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Schneider P Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Walse B SARomics Biostructures AB, Medicon Village, 22381 Lund (Sweden).
  • Schneider G Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland). gisbert.schneider@pharma.ethz.ch.
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  • 2015-10-22
Published in:
  • Angewandte Chemie (International ed. in English). - 2015
chemical biology
computational chemistry
kinases
molecular design
target prediction
Death-Associated Protein Kinases
Dose-Response Relationship, Drug
Drug Discovery
Humans
Molecular Structure
Protein Kinase Inhibitors
Structure-Activity Relationship
English Automated molecular de novo design led to the discovery of an innovative inhibitor of death-associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment-like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/58006
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