product name Elesclomol (STA-4783)
Description: Elesclomol (also known as STA-4783) is a novel potent oxidative stress inducer that elicits pro-apoptosis events among tumor cells. Elesclomol induces oxidative stress, creating high levels of reactive oxygen species (ROS), such as hydrogen peroxide, in both cancer cells and normal cells.
References: Mol Cancer Ther. 2008 Aug;7(8):2319-27; J Am Chem Soc. 2010 Apr 21;132(15):5469-78; Curr Opin Investig Drugs. 2006 Jun;7(6):574-80.
400.5
Formula
C19H20N4O2S2
CAS No.
488832-69-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 80 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: Elesclomol significantly induces the expression of heat shock stress response genes and metallothionein genes, a signature transcription profile indicative of oxidative stress in Hs294T cells. Elesclomol (100 nM) rapidly induces Hsp70 RNA levels with a 4.8-fold increase at 1 hour and a 160-fold increase at 6 hours in Ramos Burkitts lymphoma B cells in consistent with the intracellular ROS content which increases by 20% as early as 0.5 hour and 385% at 6 hours, and the induction of Hsp70 can be blocked by antioxidants N-acetylcysteine (NAC) and Tiron pretreatment. Elesclomol increases 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 cells. Elesclomol significantly inhibits the cell viability of SK-MEL-5, MCF-7, and HL-60 with IC50 of 110 nM, 24 nM and 9 nM, respectively. Elesclomol induces copper-dependent ROS generation and cytoxicity in yeast. Instead of working through a specific cellular protein target, Elesclomol interacts with the electron transport chain (ETC), a biologically coherent set of processes occurring in the mitochondrion, to generate high levels of ROS within the organelle and consequently cell death. Kinase Assay: Cell Assay: Cells are treated with various concentrations of Elesclomol for 18 or 24 hours. The level of intracellular ROS is monitored using the DCFDA probe, which emits a green fluorescence on oxidation. Cell death is determined by flow cytometry of cells double stained with Annexin V/FITC and propidium iodide (PI) using a Vybrant Apoptosis assay kit. |
|---|---|
| In Vivo | Although Elesclomol (25-100 mg/kg) as a single agent shows no antitumor activity in nude mouse xenograft models of human breast cancers (MDA435, MCF7 and ZR-75-1), lung cancer (RER) or lymphoma (U937), Elesclomol substantially enhances the efficacy of chemotherapeutic agents such as paclitaxel in these models, both in terms of tumor regression and extended survival of mice. |
| Animal model | Female CD-1 nude mice bearing established MDA435 breast cancer xenograft tumors |
| Formulation & Dosage | Dissolved in DMSO, and diluted in saline; 100 mg/kg; i.v. injection |
| References | Mol Cancer Ther. 2008 Aug;7(8):2319-27; J Am Chem Soc. 2010 Apr 21;132(15):5469-78; Curr Opin Investig Drugs. 2006 Jun;7(6):574-80. |
