TAK-243 preferentially certain to UBA1 around the related E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 decreased amounts of ubiquitylated proteins, enhanced markers of proteotoxic tension and DNA damage anxiety. In vivo, TAK-243 decreased leukemic stress and targeted leukemic stem cells without proof of toxic