MKC-3946

製品コードS8286 バッチS828601

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₁H₂₀N₂O₃S

分子量

380.46

CAS No.

1093119-54-0

Solubility (25°C)*

体外

DMSO

38 mg/mL (99.87 mM)

Ethanol

3 mg/mL (7.88 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 1 40%PEG300 2 5%Tween80 3 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。	0.63mg/ml (1.66mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.6 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 clarify; 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	MKC-3946は、強力で可溶性のIRE1αエンドリボヌクレアーゼドメイン阻害剤であり、正常な単核細胞に毒性を示すことなく、多発性骨髄腫細胞株で軽度の増殖抑制を誘発しました。
in vitro	MKC-3946 triggers modest growth inhibition in MM cell lines, without toxicity in normal mononuclear cells. Importantly, it significantly enhances cytotoxicity induced by bortezomib or 17-AAG, even in the presence of bone marrow stromal cells or exogenous IL-6. Both bortezomib and 17-AAG induce ER stress, evidenced by induction of XBP1s, which is blocked by this compound. Apoptosis induced by these agents is enhanced by this chemical, associated with increased CHOP. This compound treatment does not inhibit IRE1α kinase function or binding of activated IRE1α to TRAF2 and downstream JNK signaling.
in vivo	MKC-3946 inhibits XBP1 splicing in a model of ER stress in vivo, associated with significant growth inhibition of MM cells.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	RPMI 8226 cells
	濃度	2.5, 5, 10 μM
	反応時間	3 hours
	実験の流れ	RPMI 8226 cells are treated with or without Tm (5 μg/mL) in combination with MKC-3946 (0-10μM) for 3 hours. Total RNA is extracted; XBP1 and β-actin mRNA are evaluated by RT-PCR.
動物実験	動物モデル	CB17 SCID mice
	投薬量	100 mg/kg
	投与方法	i.p.

参考

https://pubmed.ncbi.nlm.nih.gov/22538852/

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：

Afatinib or Bevacizumab in combination with Osimertinib efficiently control tumor development in orthotopic murine models of non-small lung cancer [ PLoS One, 2024, 19(6):e0304914]	PubMed: 38935790
Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death [ Nat Commun, 2023, 14(1):2132]	PubMed: 37059720
Pharmacologic IRE1α kinase inhibition alleviates aortic dissection by decreasing vascular smooth muscle cells apoptosis [ Int J Biol Sci, 2022, 18(3):1053-1064]	PubMed: 35173538
On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm [ Cell Rep, 2022, 38(10):110490]	PubMed: 35263600
Rapid Death of Follicular B Cells and Burkitt Lymphoma Cells Effectuated by Xbp1s [ J Immunol, 2020, 204(12):3236-3247]	PubMed: 32376649

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。