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TAK-243 preferentially bound to UBA1 over the connected E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 diminished amounts of ubiquitylated proteins, amplified markers of proteotoxic worry and DNA problems worry. In vivo, TAK-243 lowered leukemic burden and targeted leukemic stem cells without the need of eviden