TAK-243 (MLN7243)

製品コードS8341 バッチS834103

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 6 mg/mL (11.54 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (9.62mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 (MLN7243) 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. This compound 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. It inhibits UAE from transferring ubiquitin to an E2 enzyme. This chemical 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 this agent is evident, as shown by a dose- and time-dependent loss of both polyubiquitin chains and mono-ubiquitylated histone H2B; however, this treatment does not affect UAE (UBE1) protein levels. It also causes accumulation of short-lived proteins such as c-Jun, c-Myc, MCL1 and p53[1].
in vivo

TAK-243 (MLN7243) treatment causes death of cancer cells and, in primary human xenograft studies. This compound 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 this compound 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/29334375/
  • https://ashpublications.org/blood/article/130/Supplement%201/1533/79599/TAK-243-a-Small-Molecule-Inhibitor-of-Ubiquitin

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：

α-Synuclein aggregates inhibit ESCRT-III through sequestration and collateral degradation [ Mol Cell, 2025, 85(18):3505-3523.e17] PubMed: 40934925
Characterization of E1 enzyme dependencies in mutant-UBA1 human cells reveals UBA6 as a novel therapeutic target in VEXAS syndrome [ Leukemia, 2025, 39(8):1997-2009.] PubMed: 40588566
The solute carrier superfamily interactome [ Mol Syst Biol, 2025, 10.1038/s44320-025-00109-1] PubMed: 40355756
19S proteasome loss regulates mitotic spindle assembly through a ubiquitin-independent degradation mechanism [ Cell Rep, 2025, 44(8):116041] PubMed: 40705606
pVHL regulates protein stability of the TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation [ Cell Mol Life Sci, 2025, 82(1):335] PubMed: 40906297
Molecular features defining the efficiency of bioPROTACs [ Commun Biol, 2025, 8(1):946] PubMed: 40542219
A bacterial genotoxin reveals a p53-proteasome-LC3 regulatory axis that drives the suppression of autophagy in cells experiencing sublethal DNA damage [ iScience, 2025, 28(4):112118] PubMed: 40212583
Ubiquitin-like modifier-activating enzyme 1 as a potential therapeutic target for aortic dissection [ Int Immunopharmacol, 2025, 145:113742] PubMed: 39637577
The vaccinia virus protein, C16, promotes the ubiquitylation and relocalization of the antiviral E3 ubiquitin-ligase, TRIM25 [ J Virol, 2025, 99(8):e0089825] PubMed: 40719442
FBXO45 restricts HIV-1 replication by inducing SQSTM1/p62-mediated autophagic degradation of Tat [ J Virol, 2025, e0191224.] PubMed: 39936917

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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