Existing BTK inhibitors directly bind to the active site of BTK and face challenges such as acquired resistance or incomplete responses over time. PROTAC-induced BTK degradation works as a novel alternative therapy for drug-resistant cancers. The latest journal Science publishes the identification of BTK mutations that are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127.
Nurix Therapeutics’ TPD compound NX-2127 is a first-in-class, dual-function small-molecule protein degrader. It drives targeted BTK and transcription factor IKAROS (IKZF1/3) degradation through ubiquitination and proteasomal degradation, adding combined benefit. NX-2127 is under development of phase I clinical trials that shows promising results and a manageable safety profile for the treatment of relapsed/ refractory B-cell malignancies.