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Updated: Dec 24, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

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Discovery of a selective inhibitor of doublecortin like kinase 1

Fleur M Ferguson1,2, Behnam Nabet1,2, Srivatsan Raghavan3,4

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

Nature Chemical Biology
|April 7, 2020
PubMed

Insights

Researchers developed DCLK1-IN-1, a chemical probe targeting Doublecortin like kinase 1 (DCLK1), a protein upregulated in pancreatic cancer. This probe helps investigate DCLK1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Chemical Biology

Background:

  • Doublecortin like kinase 1 (DCLK1) is a kinase implicated in various cancers, notably pancreatic ductal adenocarcinoma (PDAC).
  • The therapeutic potential of targeting DCLK1 remains largely unexplored due to limited understanding of its function.

Purpose of the Study:

  • To develop a selective chemical probe for the DCLK1 kinase domain.
  • To investigate the biological role of DCLK1 in pancreatic cancer models.

Main Methods:

  • Chemoproteomic profiling and structure-based design were employed to create the DCLK1 chemical probe, DCLK1-IN-1.
  • Activity of DCLK1-IN-1 was assessed in patient-derived PDAC organoid models.
  • Integrated multi-omics analyses (RNA-sequencing, proteomics, phosphoproteomics) were performed to elucidate DCLK1 inhibition effects.

Main Results:

  • A selective, in vivo-compatible chemical probe, DCLK1-IN-1, was successfully developed.
  • DCLK1-IN-1 demonstrated activity against PDAC organoid models.
  • Inhibition of DCLK1 by DCLK1-IN-1 was found to modulate proteins and pathways linked to cell motility in PDAC.

Conclusions:

  • DCLK1-IN-1 serves as a valuable chemical probe for studying DCLK1.
  • This probe facilitates further investigation into DCLK1's role in cancer biology and its potential as a therapeutic target.

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