TAK-243 (MLN7243)

製品コードS8341 バッチS834104

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C19H20F3N5O5S2
分子量 519.52 CAS No. 1450833-55-2
Solubility (25°C)* 体外 DMSO 100 mg/mL (192.48 mM)
Ethanol 3 mg/mL (5.77 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 TAK-243 (MLN7243) is a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE) with an IC50 of 1 ± 0.2 nM in the UBCH10 E2 thioester assay. It has minimal inhibitory activity in a panel of kinase and receptor assays, as well as on human carbonic anhydrase type I and type II. TAK-243 (MLN7243) induces ER stress, abrogates NFκB pathway activation and promotes apoptosis.
in vitro

TAK-243 treatment causes 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 has weaker inhibitory activity against other closely related E1 ubiquitin-like activating enzymes such as Fat10-activating enzyme (UBA6; 7 ± 3 nM), NEDD8-activating enzyme (NAE; 28 ± 11 nM), SUMO-activating enzyme (SAE; 850 ± 180 nM), ISG15-activating enzyme (UBA7; 5,300 ± 2,100 nM) and autophagy-activating enzyme (ATG7; >10,000 nM) than it does against UAE. TAK-243 inhibits UAE from transferring ubiquitin to an E2 enzyme. TAK-243 shows equally potent inhibition of the two E1 enzymes capable of activating ubiquitin (UBA6 and UAE), as indicated by comparable decreases in levels of charged USE1 and UBCH10. Downstream UAE pathway inhibition by TAK-243 is evident, as shown by a dose- and time-dependent loss of both polyubiquitin chains and mono-ubiquitylated histone H2B; however, TAK-243 treatment does not affect UAE (UBE1) protein levels. TAK-243 treatment also causes accumulation of short-lived proteins such as c-Jun, c-Myc, MCL1 and p53[1].
in vivo

TAK-243 treatment causes death of cancer cells and, in primary human xenograft studies. TAK-243 demonstrates broad antitumor activity in models of solid and hematological tumors[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HCT-116 and WSU-DLCL2 cells
濃度 0.01, 0.10 or 1.00 μM
反応時間 1, 2, 4, 8, 16 and 24 h
実験の流れ

HCT-116 and WSU-DLCL2 cells are maintained in log-phase growth in McCoy's 5A modified or RPMI-1460 medium, respectively supplemented with 10% fetal bovine serum at 37℃ in a 5% CO2 incubator. Cells are grown in 6-well cell culture dishes and treated with DMSO (0.1%) or with 0.01, 0.10 or 1.00 μM TAK-243 for the times indicated. Whole-cell extracts are prepared using RIPA buffer.
動物実験 動物モデル SCID mice bearing WSU-DLCL2 NHL xenograft tumors
投薬量 12.5, 18.75 and 25 mg/kg
投与方法 IV

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Ubiquitin-like modifier-activating enzyme 1 as a potential therapeutic target for aortic dissection [ Int Immunopharmacol, 2025, 145:113742] PubMed: 39637577
The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance [ Cell, 2024, 187(21):6055-6070.e22] PubMed: 39181133
Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function [ Cell, 2024, 187(21):5967-5980.e17] PubMed: 39276772
Caspase-2 is a condensate-mediated deubiquitinase in protein quality control [ Nat Cell Biol, 2024, 26(11):1943-1957] PubMed: 39482354
A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins [ Nat Commun, 2024, 15(1):2485] PubMed: 38509117
Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation [ Mol Cell, 2024, 84(16):3115-3127.e11] PubMed: 39116872
UBA1 inhibition sensitizes cancer cells to PARP inhibitors [ Cell Rep Med, 2024, 5(12):101834] PubMed: 39626673
PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation [ EMBO J, 2024, 43(18):3968-3999] PubMed: 39103492
Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage [ J Biomed Sci, 2024, 31(1):68] PubMed: 38992694
Cilia defects upon loss of WDR4 are linked to proteasomal hyperactivity and ubiquitin shortage [ Cell Death Dis, 2024, 15(9):660] PubMed: 39251572

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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