伊利司莫作用机制 - Medchemexpress - MCE中国

1、Product Data SheetElesclomolCat. No.: HY-12040CAS No.: 488832-69-5分式: CHNOS分量: 400.52作靶点: Apoptosis作通路: Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 22 mg/mL (54.93 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备

2、储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加

3、助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.24 mM); Clear solution此案可获得 2.5 mg/mL (6.24 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到

4、 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.24 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (6.24 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均

5、匀。BIOLOGICAL ACTIVITY物活性 Elesclomol种氧化应激诱导剂，可诱导癌细胞凋亡。体外研究 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.体内研究 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.户使本产品发表的科研献 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