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De Novo Fragment Design for Drug Discovery and Chemical Biology.

Publication ,  Journal Article
Rodrigues, T; Reker, D; Welin, M; Caldera, M; Brunner, C; Gabernet, G; Schneider, P; Walse, B; Schneider, G
Published in: Angewandte Chemie (International ed. in English)
December 2015

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.

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Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

December 2015

Volume

54

Issue

50

Start / End Page

15079 / 15083

Related Subject Headings

  • Structure-Activity Relationship
  • Protein Kinase Inhibitors
  • Organic Chemistry
  • Molecular Structure
  • Humans
  • Drug Discovery
  • Dose-Response Relationship, Drug
  • Death-Associated Protein Kinases
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

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Rodrigues, T., Reker, D., Welin, M., Caldera, M., Brunner, C., Gabernet, G., … Schneider, G. (2015). De Novo Fragment Design for Drug Discovery and Chemical Biology. Angewandte Chemie (International Ed. in English), 54(50), 15079–15083. https://doi.org/10.1002/anie.201508055
Rodrigues, Tiago, Daniel Reker, Martin Welin, Michael Caldera, Cyrill Brunner, Gisela Gabernet, Petra Schneider, Björn Walse, and Gisbert Schneider. “De Novo Fragment Design for Drug Discovery and Chemical Biology.Angewandte Chemie (International Ed. in English) 54, no. 50 (December 2015): 15079–83. https://doi.org/10.1002/anie.201508055.
Rodrigues T, Reker D, Welin M, Caldera M, Brunner C, Gabernet G, et al. De Novo Fragment Design for Drug Discovery and Chemical Biology. Angewandte Chemie (International ed in English). 2015 Dec;54(50):15079–83.
Rodrigues, Tiago, et al. “De Novo Fragment Design for Drug Discovery and Chemical Biology.Angewandte Chemie (International Ed. in English), vol. 54, no. 50, Dec. 2015, pp. 15079–83. Epmc, doi:10.1002/anie.201508055.
Rodrigues T, Reker D, Welin M, Caldera M, Brunner C, Gabernet G, Schneider P, Walse B, Schneider G. De Novo Fragment Design for Drug Discovery and Chemical Biology. Angewandte Chemie (International ed in English). 2015 Dec;54(50):15079–15083.
Journal cover image

Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

December 2015

Volume

54

Issue

50

Start / End Page

15079 / 15083

Related Subject Headings

  • Structure-Activity Relationship
  • Protein Kinase Inhibitors
  • Organic Chemistry
  • Molecular Structure
  • Humans
  • Drug Discovery
  • Dose-Response Relationship, Drug
  • Death-Associated Protein Kinases
  • 34 Chemical sciences
  • 03 Chemical Sciences