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TAK-243 preferentially sure to UBA1 around the related E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 decreased levels of ubiquitylated proteins, increased markers of proteotoxic tension and DNA harm tension. In vivo, TAK-243 lowered leukemic burden and focused leukemic stem cells with out proof of toxicity. La