| 产品介绍 |
TAK-243 (MLN7243) is a potent, selective and cell permeable small molecule inhibitor of the ubiquitin activating enzyme (UAE) at nM range. The ubiquitin-activating enzymes, found more active in cancer cells than in normal healthy cells, catalyze the first step in ubiquitination reaction, targeting a protein for degradation via proteasome. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment. TAK-243 is now in phase I clinical trials for adult patients with advanced solid tumors.
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