Sub-stoichiometric Degradation is Dispensable for Potent PROTACs: A Case Study for Irreversible Covalent BTK Degraders
Ran Cheng, Hanfeng Lin, Xin Yu, Shrilekha Misra, Andrew D. Mitchell, Jennifer Ann Woyach, Qi XL, Jin Wang
This paper develops and characterizes PSIRC3, a covalent PROTAC for BTK, showing it achieves potent degradation with sub-nanomolar potency and high selectivity, challenging the necessity of catalytic turnover for PROTAC efficacy.
bioRxiv · Feb 15, 2026 · PreprintBiochemistry