IACS-010759 (IACS-10759)

製品コードS8731 バッチS873101

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	27 mg/mL (47.99 mM)
		Water	Insoluble
		Ethanol	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	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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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：

Mitochondrial complex I promotes kidney cancer metastasis [ Nature, 2024, 10.1038/s41586-024-07812-3]	PubMed: 39143213
Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition [ Nat Commun, 2024, 15(1):8682]	PubMed: 39375345
Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously [ Nat Commun, 2024, 15(1):668]	PubMed: 38253551
Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer [ Clin Transl Med, 2024, 14(5):e1678]	PubMed: 38736108
Deoxycytidine kinase inactivation enhances gemcitabine resistance and sensitizes mitochondrial metabolism interference in pancreatic cancer [ Cell Death Dis, 2024, 15(2):131]	PubMed: 38346958
Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations [ Cell Rep, 2024, 43(10):114775]	PubMed: 39305483
Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination [ Oncogenesis, 2024, 13(1):7]	PubMed: 38272902
Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging [ Cancer Metab, 2024, 12(1):13]	PubMed: 38702787
Targeting metabolic adaptive responses induced by glucose starvation inhibits cell proliferation and enhances cell death in osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines [ Biochem Pharmacol, 2024, S0006-2952(24)00144-8]	PubMed: 38522556
Targeting Asparagine Metabolism in Well-Differentiated/Dedifferentiated Liposarcoma [ Cancers (Basel), 2024, 16(17)3031]	PubMed: 39272889

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