DETAILED NOTES ON SINEFUNGIN

TAK-243 preferentially certain to UBA1 in excess of the relevant E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 reduced levels of ubiquitylated proteins, improved markers of proteotoxic pressure and DNA destruction strain. In vivo, TAK-243 reduced leukemic burden and qualified leukemic stem cells without eviden