Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

@article{Ciceri2014DualKI,
  title={Dual kinase-bromodomain inhibitors for rationally designed polypharmacology},
  author={Pietro Ciceri and Susanne M{\"u}ller and Alison O'Mahony and Oleg Fedorov and Panagis Filippakopoulos and Jeremy P Hunt and Elisabeth A. Lasater and Gabriel Pallares and Sarah Picaud and Christopher Wells and Sarah Martin and Lisa M. Wodicka and Neil P. Shah and Daniel K. Treiber and Stefan Knapp},
  journal={Nature chemical biology},
  year={2014},
  volume={10},
  pages={305 - 312},
  url={https://api.semanticscholar.org/CorpusID:263955521}
}
It is reported that several clinical kinase inhibitors also inhibit bromodomains with therapeutically relevant potencies and are best classified as dual kinase/bromidomain inhibitors, a novel strategy for rational single agent polypharmacological targeting.
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37 Citations
Background Citations
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Methods Citations
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37 Citations

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This Review discusses kinase inhibitors for which non-kinase targets have been identified and the application of emerging techniques to validate drug–target engagement in intact cells.

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This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromidomain target validation.

Developing small molecule inhibitors of bromodomain-histone interactions

This work has provided useful structure-activity relationships for a subset of bromodomains, which will be useful in future ligand development programmes of this emerging therapeutic target class.

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Findings exemplify the potential BDF5 holds as a drug target in Leishmania and provide a foundation for the future development of optimised antileishmanial compounds targeting this epigenetic reader protein.

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An overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors are provided.

62 References

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Analysis of the interaction patterns reveals a class of 'group-selective' inhibitors broadly active against a single subfamily of kinases, but selective outside that subfamily.
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