TAK-243 preferentially sure to UBA1 above the relevant E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 lowered levels of ubiquitylated proteins, improved markers of proteotoxic stress and DNA problems worry. In vivo, TAK-243 lowered leukemic burden and focused leukemic stem cells with out evidence of toxicity. F