Development and Structural Characterization of UTE‐156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase (Adv. Sci. 25/2026)

Covalent Inhibition of VCP/p97 This frontispiece highlights the hexameric VCP/p97 AAA+ ATPase complex (blue), a central regulator of protein homeostasis. Small-molecule inhibition of VCP has emerged as a promising therapeutic strategy. UTE-156 (green) represents a covalent inhibitor targeting Cys522 within the D2 ATPase domain. This work provides structural insight into selective covalent modulation of VCP function. More details can be found in the Research Article by Peter S. Shen and co-workers (DOI: 10.1002/advs.202520545). Image credit: Daniela Tamayo Jaramillo.