Discovery and optimization of the next generation of cell active Protein Kinase Novel 3 (PKN3) inhibitors
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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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Shining light on Protein Kinase Novel 3 (PKN3), an understudied kinase with a wide array biological functions that are yet to be fully explored. We report on the design and development of a novel advanced functional chemical tool inhibitor for PKN3 URS03-06 ( 6e ). This pyridyl imidazole series has been synthesized and evaluated against PKN3 in vitro, in cells and evaluated across the kinome. The resulting compound, URS03-06 ( 6e ) is a narrow spectrum inhibitor of with an IC 50 of 210nM in cells and a narrow kinome profile S 30 =0.02 at 1μM. The discovery of URS03-06 ( 6e ) could enable the further elucidation and interrogation of PKN3 cellular biology.
