Related Experiment Video

Updated: Jul 5, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

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

Published on: May 3, 2018

18.7K

Druggable cavities and allosteric modulators of the cell division cycle 7 (CDC7) kinase

Elisa Rojas-Prats1, Loreto Martinez-Gonzalez1,2, Carmen Gil1

  • 1Centro de Investigaciones Biológicas -Margarita Salas-CSIC, Madrid, Spain.

Journal of Enzyme Inhibition and Medicinal Chemistry
|January 11, 2024
PubMed

Insights

Researchers identified novel allosteric inhibitors for cell division cycle 7 kinase (CDC7), a target for cancer and neurodegenerative diseases. These selective CDC7 modulators offer a promising new therapeutic avenue beyond traditional ATP-competitive drugs.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Cell division cycle 7 kinase (CDC7) is overexpressed in cancers and implicated in TDP-43 phosphorylation, a hallmark of neurodegenerative diseases.
  • Existing CDC7 inhibitors are ATP-competitive, limiting their clinical efficacy due to insufficient selectivity.
  • Allosteric modulation of CDC7 presents a significant opportunity for developing more selective and effective therapeutics.

Purpose of the Study:

  • To identify novel druggable allosteric sites on human CDC7.
  • To discover selective CDC7 inhibitors that modulate its activity through allosteric mechanisms.
  • To explore new therapeutic strategies for oncological and neurodegenerative disorders targeting CDC7.

Main Methods:

  • Utilized computational approaches to analyze the human CDC7 structure.
  • Identified and characterized new druggable cavities within the CDC7 protein.
  • Designed and proposed allosteric modulators targeting specific interaction pockets.

Main Results:

  • Discovered novel allosteric binding sites on the human CDC7 kinase.
  • Identified potential selective CDC7 inhibitors with allosteric modulation capabilities.
  • Targeted pockets involved in the interaction between CDC7 and its activator DBF4.

Conclusions:

  • Computational methods can effectively identify allosteric sites and inhibitors for CDC7.
  • Allosteric CDC7 inhibitors offer a promising alternative to ATP-competitive drugs.
  • This research paves the way for developing novel treatments for cancer and neurodegenerative diseases.
Keywords:
CDC7DBF4allosteric modulatorbinding pocketsvirtual screening

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