Related Experiment Video

Updated: Jun 26, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Cyclin-dependent kinase-inhibitor screening and structural analysis identify a CDK-like kinase candidate in Naegleria

Min-Jeong Kim1, Joo Hwan No2,3

  • 1Department of Parasitology, School of Medicine, Chungbuk National University, Cheongju, Republic of Korea.

Parasites & Vectors
|June 25, 2026
PubMed
Abstract

Insights

This study screened CDK inhibitors against Naegleria fowleri, identifying potent compounds and a potential drug target. These findings offer new avenues for treating primary amebic meningoencephalitis (PAM).

Area of Science:

  • Parasitology
  • Drug Discovery
  • Structural Biology

Background:

  • Primary amebic meningoencephalitis (PAM) is a fatal infection caused by Naegleria fowleri with limited treatment options.
  • Investigating Cyclin-Dependent Kinase (CDK)-related pathways in N. fowleri is crucial for developing new therapies.

Purpose of the Study:

  • To screen a library of CDK inhibitors against N. fowleri.
  • To identify potential drug targets within N. fowleri's CDK-like proteins.

Main Methods:

  • Screening 126 CDK inhibitors using a luminescence-based ATP viability assay.
  • Performing sequence analysis, homology modeling, molecular docking, and molecular dynamics simulations on Nf_CDK-like protein1.
  • Utilizing human CDK sequences for BLASTp searches against the N. fowleri proteome.

Main Results:

  • Twenty-three active CDK inhibitors were identified, with five showing submicromolar activity (AZD5438, GSK-3 inhibitor IX, milciclib, roniciclib, SU9516).
  • Nf_CDK-like protein1 was identified with high similarity to Trypanosoma brucei CRK3 and conserved kinase features.
  • Docking and molecular dynamics simulations indicated stable interactions between prioritized compounds and the Nf_CDK-like protein1 ATP-binding site.

Conclusions:

  • Multiple CDK inhibitor scaffolds exhibit potent in vitro activity against N. fowleri.
  • Nf_CDK-like protein1 is a potential CDK-like kinase target for anti-amoebic drug development.
  • CDK-like pathways represent a viable target for structure-guided optimization of anti-amoebic candidates.
Keywords:
Naegleria fowleriCyclin-dependent kinaseDrug repurposingMolecular dockingMolecular dynamicsPrimary amebic meningoencephalitis

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