TAK-243

TAK-243 (MLN7243) is a first-in-class, selective ubiquitin activating enzyme, UAE (UBA1) inhibitor (IC₅₀=1 nM), which blocks ubiquitin conjugation, disrupting monoubiquitin signaling as well as global protein ubiquitination. TAK-243 (MLN7243) induces endoplasmic reticulum (ER) stress, abrogates NF-κB pathway activation and promotes apoptosis^[1][2]. IC50 & Target: IC50: 1 nM (UBA1)^[1] In Vitro: TAK-243 shows anti-proliferative effect on a panel of cell lines derived from hematologic and solid tumors with variable EC₅₀ values that ranged from 0.006 µM to 1.31 µM^[1].
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 IC₅₀s ranging from 15-40 nM after treatment for 48 hours^[3]. 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^[3].