伊利司莫作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetElesclomolCat. No.: HY-12040CAS No.: 488832-69-5分式: CHNOS分量: 400.52作靶點(diǎn): Apoptosis作通路: Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 22 mg/mL (54.93 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備

2、儲備液1 mM 2.4968 mL 12.4838 mL 24.9675 mL5 mM 0.4994 mL 2.4968 mL 4.9935 mL10 mM 0.2497 mL 1.2484 mL 2.4968 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時(shí)，請?jiān)?6 個(gè)內(nèi)使，-20C 儲存時(shí)，請?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加

3、助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.24 mM); Clear solution此案可獲得 2.5 mg/mL (6.24 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到

4、 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.24 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.24 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均

5、勻。BIOLOGICAL ACTIVITY物活性 Elesclomol種氧化應(yīng)激誘導(dǎo)劑，可誘導(dǎo)癌細(xì)胞凋亡。體外研究 Elesclomol significantly induces the expression of heat shock stress response genes and metallothionein genes, asignature transcription profile indicative of oxidative stress in Hs294T cells. Elesclomol (100 nM) rapidly induces Hsp70RNA level

6、s with a 4.8-fold increase at 1 hour and a 160-fold increase at 6 hours in Ramos Burkitts lymphoma B cellsin consistent with the intracellular ROS content which increases by 20% as early as 0.5 hour and 385% at 6 hours, andthe induction of Hsp70 can be blocked by antioxidants N-acetylcysteine (NAC)

7、and Tiron pretreatment. Elesclomolincreases the number of early and late apoptotic cells with 3.7- and 11-fold through the induction of oxidative stress,which can be completely blocked by NAC, while having little effect on normal cells1. Elesclomol significantly inhibitsthe cell viability of SK-MEL-

8、5, MCF-7, and HL-60 with IC50 of 110 nM, 24 nM and 9 nM, respectively2. Elesclomolinduces copper-dependent ROS generation and cytoxicity in yeast. Instead of working through a specific cellularprotein target, elesclomol interacts with the electron transport chain (ETC), a biologically coherent set o

9、f processesoccurring in the mitochondrion, to generate high levels of ROS within the organelle and consequently cell death3.體內(nèi)研究 Although elesclomol (25-100 mg/kg) shows no antitumor activity in nude mouse xenograft models of human breast cancers (MDA435, MCF7 and ZR-75-1), lung cancer (RER) or lymp

10、homa (U937). Elesclomol substantially enhances the efficacy of chemotherapeutic agents such as paclitaxel in these models, both in terms of tumor regression andextended survival of mice4.PROTOCOLCell Assay 3 For viability assays, HBL and HBL-0 cells are incubated with 300 nM elesclomol-Cu or Cu for

11、24 h. Cell death isdetermined using propidium iodide (5 g/mL in PBS) staining and FACS analysis. Inner mitochondrial transmembranepotential is measured by incubating cells (25104/mL) with 40 nM DIOC6(3) for 15 minutes at 37C immediately priorto flow cytometry.MCE has not independently confirmed the

12、accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Chem Biol. 2019 Jul;15(7):681-689. Biomolecules. 2019 Jul 24;9(8). pii: E298. bioRxiv. March 24, 2018. Patent. US9808434B2. Patent. US20160354327A1.See more customer validations on HYPERLINK www.MedChemE www.MedChemEPage 2 of 3 w

13、ww.MedChemEREFERENCES1. Kirshner JR, et al. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 2008 Aug;7(8):2319-27.2. 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):5469-73. Blackman RK, et al. Mitochondrial electron transport is the cellular target of the oncology drug elesclomol. PLoS One. 2012;7(1):e29798.4. Gehrmann M. Drug evaluation: STA-4783-enhancing taxane efficacy by induction of Hsp70. Curr Opin Investig Drugs. 2006 Jun;7(6):574-80.McePdfHeightC