TAK-243

TAK-243 is a first-in-class, small molecule inhibitor of the ubiquitin activating enzyme (UAE), also known as ubiquitin E1 enzyme (UBA1). Developed by Takeda Oncology and Millennium, it binds to and inhibits UAE/UBA1, preventing protein ubiquitination and subsequent proteasomal degradation. This leads to accumulation of proteins in cells, induction of endoplasmic reticulum stress, activation of the unfolded protein response, impairment of DNA damage repair pathways, and ultimately apoptosis. TAK-243 has demonstrated potent antineoplastic activity in preclinical models across several cancer types including acute myeloid leukemia (AML) and adrenocortical carcinoma (ACC), with evidence for synergy when combined with other anticancer agents such as BCL2 inhibitors or standard chemotherapies. It is currently being evaluated in phase I clinical trials for advanced solid tumors and hematologic malignancies[1][2][5][6][7][9].

Other names

uae inhibitor MLN7243