Proteolytic Targeting Chimeras (PROTACs) for Targeting LCK-driven Leukemia (SJ-21-0047)

St. Jude Reference #SJ-21-0047


LCK is an emerging therapeutic target for T-ALL. Dasatinib, a small-molecule LCK inhibitor, has significant anti-leukemia efficacy in vitro and in vivo against T-ALL. However, these effects require constant dosing of dasatinib and drug resistance is common. The PROTACs we developed showed greater potency and longer-lasting effects than dasatinib in suppressing LCK signaling and thus better cytotoxity in LCK-dependent T-ALLs.

Researchers at St. Jude created a series of Proteolytic Targeting Chimera (PROTACs) compounds that can target LCK for degradation with dasatinib as the bait/ligand. LCK kinase is an important drug target in T-ALL and these PROTACs induce T-ALL apoptosis by complete degradation of therapeutic target LCK. 


small molecule, drug, PROTAC. targeted protein degradation, Dasatinib, LCK inhibitor, leukemia, T-ALL, resistance.

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