DETAILS, FICTION AND A 83-01

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TAK-243 preferentially bound to UBA1 more than the relevant E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 lessened amounts of ubiquitylated proteins, amplified markers of proteotoxic tension and DNA hurt strain. In vivo, TAK-243 minimized leukemic stress and specific leukemic stem cells with no evidence of tox