TAK-243 preferentially bound to UBA1 over the similar E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 diminished amounts of ubiquitylated proteins, enhanced markers of proteotoxic strain and DNA hurt anxiety. In vivo, TAK-243 lowered leukemic load and targeted leukemic stem cells without proof of toxicity. Event