Biological Activity
TAK-243 is a potent and selective ubiquitin-like modifier activating enzyme 1 (UBA1) inhibitor.
In Vitro
TAK-243 (MLN7243) selectively kills a subset of cutaneous squamous cell carcinoma (cSCC) lines. squamous cell carcinoma transplant (SCCT) and SCCRDEBMet cells are the most susceptible to continuous treatment with TAK-243. SCCIC1Met cells are also selectively killed by an extended exposure to TAK-243. Death in SCCRDEBMet cells displays the greatest sensitivity to a pulse of TAK-243. MLN7243 can reduce the cellular level of ubiquitin conjugates. TAK-243 decreases UBA1 and UBA6 thioesters and thioesters of the UBA6 specific E2 UBE2Z/USE1[1]. TAK-243 displays preferential activity towards acute myeloid leukemia (AML) cells over normal hematopoietic cells. TAK-243 reduces growth and viability of human AML cell lines (OCI-AML2, TEX, U937 and NB4) in a concentration- and time-dependent manner with IC50 's ranging from 15-40 nM after treatment for 48 hours[2].
In Vivo
TAK-243 significantly delays tumor growth in mice (T/C=0.02) with no toxicity as evidenced by no changes in mouse body weight, serum chemistry, or organ histology. TAK-243 reduces primary AML tumor burden in both tested samples without toxicity[2].
References & source
[1]. Hyer ML, et al. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat Med. 2018 Feb;24(2):186-193.
[2]. Best SR, et al. TAK-243, a small molecule inhibitor of ubiquitin-activating enzyme (UAE), induces ER stress and
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.