DETAILED NOTES ON SINEFUNGIN

TAK-243 preferentially bound to UBA1 more than the associated E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 reduced amounts of ubiquitylated proteins, improved markers of proteotoxic pressure and DNA damage pressure. In vivo, TAK-243 diminished leukemic burden and qualified leukemic stem cells without proof of