SJ001011646

SJ001011646 is a proteolysis-targeting chimera (PROTAC) designed to induce the degradation of the lymphocyte-specific protein tyrosine kinase (LCK). Developed by researchers at St. Jude Children's Research Hospital, the molecule functions by recruiting LCK to the cereblon (CRBN) E3 ubiquitin ligase, leading to the ubiquitination and subsequent proteasomal degradation of the target protein. This approach is intended to provide more sustained suppression of LCK signaling compared to traditional small-molecule inhibitors like dasatinib. SJ001011646 has demonstrated potent anti-leukemic activity in preclinical models of T-cell acute lymphoblastic leukemia (T-ALL), particularly in cases exhibiting LCK dependency, showing significantly improved duration of target suppression and cytotoxic effects in patient-derived samples.