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25mg |
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1g |
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Purity: ≥98%
TPEN (also known as TPED) is a specific cell-permeable heavy metal chelator. TPEN targets colon cancer cells through redox cycling of copper. TPEN reduced cell viability in a dose- and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of γ-H2AX protein and activation of ATM/ATR signaling pathway. Cell death by TPEN was dependent on ROS generation as evidenced by the reversal of cell viability, and DNA damage and the abrogation of γ-H2AX levels in the presence of antioxidants. TPEN-induced cell death was also dependent on the redox cycling of copper since the copper chelator neocuproine inhibited DNA damage and reduced pChk1, γ-H2AX, and ATM protein expression. Cell death by low TPEN concentrations, involved ATM/ATR signaling in all 3 cell lines, since pre-incubation with specific inhibitors of ATM and DNA-PK led to the recovery of cells from TPEN-induced DNA damage.
ln Vitro |
Cadmium, mercury, and methylmercury all elicit alterations in fura-2 fluorescence that are attenuated by the heavy metal chelator TPEN. TPEN is a low-affinity Ca2+-cation chelator for heavy metals that is cell-permeable. When 10 or 30 μM cadmium chloride was added to cells, the elevated fura-2 fluorescence ratio was significantly reduced to basal levels within 10 minutes (ΔRatio decreased by 119.6±2.4% or 109±1.5% (F340/F380) induced by 10 or 30 μM cadmium chloride, respectively). This suggests that the increase in fura-2 fluorescence ratio caused by cadmium chloride is dependent on intracellular heavy metal cations rather than intracellular Ca2+ [1]. TPEN is a metal chelator that uses copper redox cycling to target colon cancer cells. TPEN decreased cell viability in a way that was dependent on both dose and time. Copper redox cycling is also necessary for TPEN-induced cell death since the copper chelator neocuproline prevents DNA damage and lowers the expression of the ATM, γ-H2AX, pChk1, and other proteins. All three of the cell lines exhibit ATM/ATR signaling in response to low TPEN concentrations; however, preincubation with certain ATM and DNA-PK inhibitors prevented TPEN-induced DNA damage from occurring in the cells [2].
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ln Vivo |
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Animal Protocol |
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References |
[1]. Ohkubo M, et al. Heavy metal chelator TPEN attenuates fura-2 fluorescence changes induced by cadmium, mercury and methylmercury. J Vet Med Sci. 2016 Jun 1;78(5):761-7.
[2]. Rahal ON, et al. Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells. Cancer Biol Ther. 2016 Nov;17(11):1139-1148. [3]. E Aizenman, et al. Induction of neuronal apoptosis by thiol oxidation: putative role of intracellular zinc release. J Neurochem. 2000 Nov;75(5):1878-88 |
Molecular Formula |
C26H28N6
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Molecular Weight |
424.55
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CAS # |
16858-02-9
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
N(CC1=NC=CC=C1)(CC2=NC=CC=C2)CCN(CC3=NC=CC=C3)CC4=NC=CC=C4
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Chemical Name |
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.3554 mL | 11.7772 mL | 23.5544 mL | |
5 mM | 0.4711 mL | 2.3554 mL | 4.7109 mL | |
10 mM | 0.2355 mL | 1.1777 mL | 2.3554 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
TPEN decreases the viability and induces DNA damage in human colon cancer cell lines.Cancer Biol Ther.2016 Nov;17(11):1139-1148. th> |
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DNA damage by TPEN is dependent on ROS.Cancer Biol Ther.2016 Nov;17(11):1139-1148. td> |
DNA damage by TPEN is dependent on redox cycling of copper.Cancer Biol Ther.2016 Nov;17(11):1139-1148. td> |
TPEN-induced cell death involves Chk1, DNA-PK and ATM.Cancer Biol Ther.2016 Nov;17(11):1139-1148. th> |
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Silencing Chk1 and DNA-PK inhibits TPEN-induced apoptosis.Cancer Biol Ther.2016 Nov;17(11):1139-1148. td> |
Effect of TPEN on fura-2 fluorescence changes induced by stimulation with cadmium chloride, mercury chloride or MeHg.J Vet Med Sci.2016 Jun 1;78(5):761-7. td> |