DETAILS, FICTION AND PRT062607 HYDROCHLORIDE

TAK-243 preferentially sure to UBA1 in excess of the connected E1 enzymes UBA2, UBA3, and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 diminished levels of ubiquitylated proteins, amplified markers of proteotoxic stress and DNA injury tension. In vivo, TAK-243 decreased leukemic load and targeted leukemic stem cells without the need of