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 decreased levels of ubiquitylated proteins, improved markers of proteotoxic strain and DNA damage stress. In vivo, TAK-243 lowered leukemic load and focused leukemic stem cells without proof of toxicity. Last b