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Discovery and optimization of the next generation of cell active Protein Kinase Novel 3 (PKN3) inhibitors

Georgiou, E.; Laitinen, T.; Poso, A.; Heino, R.; Asquith, C. R. M.

2026-08-20 pharmacology and toxicology
10.64898/2026.08.20.745975 bioRxiv
Show abstract

Protein Kinase Novel 3 (PKN3) understudied kinase with a diverse array of biological functions that are yet to be fully defined. Here, we report the design and development of a novel advanced functional chemical tool inhibitor for PKN3. A pyridyl imidazole series has been synthesized and evaluated against PKN3 in vitro and in cells. These efforts led to the discovery of 6e (URS03-06), a submicromolar cell active functional inhibitor with a narrow kinome spectrum, to enable the elucidation and interrogation of PKN3 cellular biology.

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