What question did this study set out to answer?

The aim is to identify small molecule inhibitors that target β-hematin formation and Pf PKG in Plasmodium falciparum.

February 19, 2026ChemMedChem1 citations

Small Molecule Kinase Inhibitors with In Vitro β‐Hematin Formation and Plasmodium falciparum Protein Kinase G Inhibitory Activity Identified Using Machine Learning

JTJessica ThibaudStellenbosch University NSNicolaas SalomaneUniversity of Cape Town SHSarah HarriesUniversity of Cape Town

Key Points

The aim is to identify small molecule inhibitors that target β-hematin formation and Pf PKG in Plasmodium falciparum.
Screened the BioVision Protein Kinase Inhibitor library using molecular docking and machine learning.
Focused on identifying compounds that inhibit both β-hematin formation and Pf PKG.
Evaluated inhibitory activity by measuring IC50 values for identified compounds.
Three compounds showed promising dual activity against both targets: derazantinib, pazopanib, and afatinib.
Derazantinib had the lowest IC50 value at 88 µM for β-hematin and 0.160 µM for Pf PKG.
Pazopanib and afatinib exhibited higher IC50 values, suggesting less potency.

Abstract

Using a combination of molecular docking and machine learning, the BioVision Protein Kinase Inhibitor library was screened for potential inhibitors with dual activity against two Plasmodium falciparum targets, β‐hematin (synthetic hemozoin) formation and cGMP‐dependent protein kinase ( Pf PKG). Three compounds with promising activity against both targets were identified. Derazantinib is the most potent hit compound with IC 50 values of 88 µM for inhibition of β‐hematin formation (compared to 22 μM for chloroquine) and 0.160 µM against Pf PKG. Pazopanib (β‐hematin IC 50 : 219 µM and Pf PKG IC 50 : 0.330 µM) and afatinib (234 and 2.61 µM, respectively) showed more moderate activity profiles against both targets.

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