Elesclomol (Synonyms: 伊利司莫; STA-4783)
Elesclomol (STA-4783) 是一種有效的銅離子載體，可促進銅死亡 (cuproptosis)。Elesclomol 特異性結合鐵氧還蛋白 1 (FDX1) α2/α3 螺旋和 β5 鏈，抑制 FDX1 介導的 Fe-S 簇生物合成。Elesclomol 是一種氧化應激誘導劑，可誘導ai細胞凋亡。Elesclomol 是一種活性氧 (ROS) 誘導劑。Elesclomol 可用于 Menkes 和相關的遺傳性銅缺乏癥研究。
生物活性
Elesclomol (STA-4783) is a potent copper ionophore and promotes copper-dependent cell death (cuproptosis). Elesclomol specifically binds ferredoxin 1 (FDX1) α2/α3 helices and β5 strand. Elesclomol inhibits FDX1-mediated Fe-S cluster biosynthesis. Elesclomol is an oxidative stress inducer that induces cancer cell apoptosis. Elesclomol is a reactive oxygen species (ROS) inducer. Elesclomol can be used for Menkes and associated disorders of hereditary copper deficiency research[1][2][3][4].
體外研究(In Vitro)
Elesclomol (STA-4783) binds the FDX1 α2/α3 helices and β5 strand, but does not bind the paralog protein FDX2. Elesclomol-Cu(II) is an FDX1 neo-substrate. FDX1 protein binds and reduces the elesclomol-Cu(II) complex[1].
Elesclomol-Cu (1:1 ratio) (40 nM) for only 2 hours results in a 15- to 60-fold increase in intracellular copper levels that triggered cell death more than 24 hours later in ABC1 cells[1].
The addition of copper to elesclomol at a 1:1 molar ratio prior to treatment significantly reduces cell viability when cells are grown in glycolytic (glucose media) conditions[2].
Elesclomol (200 nM; 18 hours) treatment increases the number of early and late apoptotic cells in HSB2 cells. Elesclomol induces apoptosis in cancer cells through the induction of oxidative stress[3].
Elesclomol significantly inhibits the cell viability of SK-MEL-5, MCF-7, and HL-60 cells with IC50 values of 110 nM, 24 nM and 9 nM, respectively[5].
Apoptosis Analysis[3]
| Cell Line: | HSB2 cells |
| Concentration: | 200 nM |
| Incubation Time: | 18 hours |
| Result: | Increased the number of early and late apoptotic cells. |
體內研究(In Vivo)
Elesclomol (10 mg/kg; subcutaneous injection; every three days from post-natal day 5 to 26 and once weekly until post-natal day 54) treatment ameliorates severe cardiac pathology with a partial reduction in hypertrophy. Cardiac [Cu] increased with Elesclomol treatment from a vehicle knockout level of 34 to 55%[4].
Elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Elesclomol prevents detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse[4].
| Animal Model: | Cardiac Ctr1 knockout mice[4] |
| Dosage: | 10 mg/kg |
| Administration: | Subcutaneous injection; every three days from post-natal day 5 to 26 and once weekly until post-natal day 54 |
| Result: | Ameliorated severe cardiac pathology with a partial reduction in hypertrophy. |
分子量：400.52
Formula：C19H20N4O2S2
CAS 號：488832-69-5
中文名稱：伊利司莫
運輸條件
Room temperature in continental US; may vary elsewhere.
儲存方式
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
溶解性數據
DMSO : 100 mg/mL (249.68 mM; Need ultrasonic)
| 濃度溶劑體積質量 | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4968 mL | 12.4838 mL | 24.9675 mL |
| 5 mM | 0.4994 mL | 2.4968 mL | 4.9935 mL |
| 10 mM | 0.2497 mL | 1.2484 mL | 2.4968 mL |
請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 儲存時，請在 6 個月內使用，-20°C 儲存時，請在 1 個月內使用。
以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
——為保證實驗結果的可靠性，澄清的儲備液可以根據儲存條件，適當保存；體內實驗的工作液，建議您現用現配，當天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的方式助溶
- 1.
請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (6.24 mM); Clear solution
- 2.
請依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (6.24 mM); Clear solution
參考文獻
[1]. Peter Tsvetkov, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022 Mar 18;375(6586):1254-1261.
[2]. Peter Tsvetkov, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019 Jul;15(7):681-689.
[3]. Kirshner JR, et al. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 2008 Aug;7(8):2319-27.
[4]. Liam M Guthrie, et al. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science. 2020 May 8;368(6491):620-625.
[5]. Bair JS, et al. Chemistry and biology of deoxynyboquinone, a potent inducer of cancer cell death. J Am Chem Soc. 2010 Apr 21;132(15):5469-7
注：產品僅用于科研
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