Elesclomol

• Catalog No.: S1052
• CAS Number: 488832-69-5
• M. F.: C19H20N4O2S2
• M. W.: 400.5177
• Storage: -20°C

SYNONYMS

• IUPAC name: 1-N',3-N'-dibenzenecarbothioyl-1-N',3-N'-dimethylpropanedihydrazide
• IUPAC Traditional name: 1-N',3-N'-dibenzenecarbothioyl-1-N',3-N'-dimethylpropanedihydrazide
• Synonyms: STA-4783

DATABASE IDS

• CAS Number: 488832-69-5

PROPERTIES

• Target: HSP
• Salt Data: Free Base
• Solubility: DMSO
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Cancer

Biological Activity

• Description: Elesclomol (STA-4783) is a novel potent oxidative stress inducer that illicits pro-apoptosis events among tumor cells..
• In Vitro: 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 Burkitt’s 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. ^[1] 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. ^[2] 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. ^[3]
• 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. ^[4]
• Clinical Trials: Currently under Phase I study of Elesclomol Sodium in patients with relapsed or refractory acute myeloid leukemia

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: Hs294T, HSB2, and Ramos
• Concentrations: Dissolved in DMSO at a concentration of 10 mM, final concentrations ~500 nM
• Incubation Time: 18, or 24 hours
• Methods: 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.
• Protocol: Animal Study ^[4]
• Animal Models: Female CD-1 nude mice bearing established MDA435 breast cancer xenograft tumors
• Formulation: Dissolved in DMSO, and diluted in saline
• Doses: ~100 mg/kg
• Administration: Intravenous injection

References

• References: [1] Kirshner JR, et al. Mol Cancer Ther, 2008, 7(8), 2319-2327.
• References: [2] Bair JS, et al. J Am Chem Soc, 2010, 132(15, 5469-5478.
• References: [3] Blackman RK, et al. PLoS One, 2012, 7(1), e29798.
• References: [4] Gehrmann M. Curr Opin Investig Drugs, 2006, 7(6), 574-580.

REFERENCES

• Bair JS, et al. J Am Chem Soc, 2010, 132(15, 5469-5478.
• Kirshner JR, et al. Mol Cancer Ther, 2008, 7(8), 2319-2327.
• Blackman RK, et al. PLoS One, 2012, 7(1), e29798.
• Gehrmann M. Curr Opin Investig Drugs, 2006, 7(6), 574-580.