IACS-010759 (IACS-10759)

製品コードS8731 バッチS873106

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₅H₂₅F₃N₆O₄S

分子量

562.56

CAS No.

1570496-34-2

Solubility (25°C)*

体外

DMSO

33 mg/mL (58.66 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

0.5mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 10 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 it; 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	IACS-010759 (IACS-10759) is a potent and selective oxidative phosphorylation inhibitor (IC50 < 10 nM) that blocks cellular respiration through inhibition of complex I.
in vitro	IACS-010759 significantly reduced viability measured by CTG assay in all cell lines tested (Notch mutant: Pf382, 1301, Jurkat, MOLT-4, P12-Ichikawa and Notch wt: T-ALL1). Treatment of T-ALL with IACS-010759 had effectively inhibited FA-stimulated mitochondrial respiration indicated by decreased oxygen consumption rates (OCR). However, the cells maintain an ability to generate energy via glycolysis, indicated by high extracellular acidification rate (ECAR) in both, control and IACS-treated groups^[1]. In CLL cells, IACS-010759 causes minimal cell death, inhibits oxygen consumption rate (OCR) and increases glycolysis. It also decreases intracellular ribonucleotide triphosphate pools in CLL^[2]. In sensitive AML cells IACS-010759 induces AMPK activation leading to mTOR suppression which results in cell growth inhibition in AML cells. AMPK and mTOR could be putative biomarkers of anti-leukemia activity of the novel OxPhosi IACS-010759^[3].
in vivo	IACS-010759 is a potent inhibitor of mitochondria complex I of the electron transport chain. It inhibits proliferation and induces apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on oxidative phosphorylation.^[4]

製品説明

IACS-010759 (IACS-10759) is a potent and selective oxidative phosphorylation inhibitor (IC50 < 10 nM) that blocks cellular respiration through inhibition of complex I.

in vitro

IACS-010759 significantly reduced viability measured by CTG assay in all cell lines tested (Notch mutant: Pf382, 1301, Jurkat, MOLT-4, P12-Ichikawa and Notch wt: T-ALL1). Treatment of T-ALL with IACS-010759 had effectively inhibited FA-stimulated mitochondrial respiration indicated by decreased oxygen consumption rates (OCR). However, the cells maintain an ability to generate energy via glycolysis, indicated by high extracellular acidification rate (ECAR) in both, control and IACS-treated groups^[1].

In CLL cells, IACS-010759 causes minimal cell death, inhibits oxygen consumption rate (OCR) and increases glycolysis. It also decreases intracellular ribonucleotide triphosphate pools in CLL^[2].

In sensitive AML cells IACS-010759 induces AMPK activation leading to mTOR suppression which results in cell growth inhibition in AML cells. AMPK and mTOR could be putative biomarkers of anti-leukemia activity of the novel OxPhosi IACS-010759^[3].

in vivo

IACS-010759 is a potent inhibitor of mitochondria complex I of the electron transport chain. It inhibits proliferation and induces apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on oxidative phosphorylation.^[4]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	CLL cells
	濃度	30 nM, 100 nM, 300 nM, 1 μM, and 3 μM
	反応時間	24 or 48 h
	実験の流れ	CLL cells are treated with IACS-010759 for 24 or 48 h and were then stained with acridine orange and analyzed by flow cytometry.
動物実験	動物モデル	Male SD rats
	投薬量	0.3 mg/kg
	投与方法	i.v.

参考

[4] Molina JR, et al. Nat Med. 2018 Jul;24(7):1036-1046.

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Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331]	PubMed: 36409827
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Targeting mitochondrial energetics reverses panobinostat- and marizomib-induced resistance in pediatric and adult high-grade gliomas [ Mol Oncol, 2023, 17(9):1821-1843]	PubMed: 37014128

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。