Chemoproteomics discovery of a CNS-penetrant covalent inhibitor of PIKfyve
Antony J. Burton, Louis S. Chupak, Alison J Davis, Ahmed S.A. Mady, Mirco Meniconi, Barry J. Teobald, Bryan W. Dorsey, Lauren R Byrne, Ryan M. Mulhern, Berent Lundeen, Elizabeth W. Sorensen, Bharti Patel, Sean Brennan, Dhiraj Kormocha, Rubén Tommasi, , Elayne Chan-Penebre
This paper discovers and optimizes a CNS-penetrant covalent inhibitor of PIKfyve, DUN058, showing sustained target occupancy and modulation of protein clearance pathways in vivo.
bioRxiv · Jan 28, 2026 · PreprintBiochemistry