ArticleACS chemical biology2026
p21-Activated Kinase (PAK) Group I-Targeting Inhibitors Promote the Dimeric Conformation in Live Cells.
Article in ACS chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
p21-activated kinases (PAKs) are involved in a broad range of cellular processes and are emerging drug targets. The human PAK family consists of 6 kinases, divided into group I (PAK1-3) and group II (PAK4-6), both families are regulated by distinct activation mechanisms and interaction partners. Currently, there are no assays available enabling the study of on-target activity for all PAK isoforms in cells. To this end, we developed a series of NanoLuc- and HaloTag-based bioluminescence resonance energy transfer assays to quantify inhibitor target engagement and dimerization of PAK isoforms in living cells. Interestingly, we found evidence that inhibitors might promote the formation of group I PAK dimers. Thus, our data uncovered a live-cell mechanism by which inhibitors modulate this dimeric conformation and provide new tools for future PAK inhibitor design.
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