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Updated: Jun 15, 2025

Identification of Kinase-substrate Pairs Using High Throughput Screening
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Identification of Kinase-substrate Pairs Using High Throughput Screening

Published on: August 29, 2015

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The prospect of substrate-based kinase inhibitors to improve target selectivity and overcome drug resistance

Biswajit Biswas1, Yen-Hua Huang1, David J Craik1

  • 1Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland Brisbane QLD 4072 Australia 4072 c.wang@imb.uq.edu.au d.craik@imb.uq.edu.au.

Chemical Science
|August 26, 2024
PubMed

Insights

Targeting protein kinase substrate sites offers a promising strategy to overcome drug resistance in cancer therapy. Emerging technologies are advancing substrate-based inhibition for more resilient kinase inhibitors.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Protein kinases are crucial drug targets in cancer therapy, with over 80 FDA-approved inhibitors.
  • Most current kinase inhibitors target ATP binding, but drug resistance due to mutations is a significant challenge.
  • Substrate site inhibition presents an alternative, potentially more selective and resistance-resilient approach.

Purpose of the Study:

  • To review recent advancements in substrate-based protein kinase inhibition.
  • To explore the potential of these approaches in overcoming drug resistance.
  • To highlight emerging technologies enabling substrate site targeting.

Main Methods:

  • Review of recent scientific literature on kinase inhibitors and drug resistance.
  • Discussion of emerging technologies like recombinant display and lead compound stabilization.
  • Analysis of substrate-based inhibition strategies.

Main Results:

  • Emerging technologies are making substrate site targeting more feasible.
  • Substrate-based inhibition holds promise for developing resistance-resilient kinase inhibitors.
  • Advances in drug discovery are expanding options beyond ATP-competitive inhibition.

Conclusions:

  • Substrate-based kinase inhibition is an evolving field with significant therapeutic potential.
  • Targeting the substrate site can offer a more durable solution to kinase-driven cancers.
  • Continued research and technological development are key to realizing this potential.

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