TPEN

Names

[ Name ]:
TPEN

[Synonym ]:
n,n,n',n'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine
N,N,N',N'-Tetrakis(2-pyridinylmethyl)-1,2-ethanediamine
N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine
MFCD00036918
N,N,N',N'-Tetrakis(pyridin-2-ylmethyl)ethane-1,2-diamine
N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine
N,N,N',N'-tetrakis-(2-Pyridylmethyl)ethylenediamine
N1,N1,N2,N2-Tetrakis(pyridin-2-ylmethyl)ethane-1,2-diamine
1,2-Ethanediamine, N,N,N,N-tetrakis(2-pyridinylmethyl)-
N,N,N′,N′-tetrakis(2-pyridylmethyl)ethane-1,2-diamine
TPEN

Biological Activity

[Description]:

TPEN is a specific cell-permeable heavy metal chelator.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Research Areas >> Cancer

[In Vitro]

Heavy metal chelator TPEN attenuates fura-2 fluorescence changes induced by cadmium, mercury and methylmercury. TPEN, a cell-permeable chelator for heavy metal cations with a low affinity for Ca2+. In cells stimulated with 10 or 30 μM cadmium chloride, the addition of TPEN at 3 hr after exposure significantly decreases the elevated fura-2 fluorescence ratio to the basal levels within 10 min (119.6±2.4% or 109±1.5% decrease in ΔRatio (F340/F380) induced by 10 or 30 μM cadmium chloride, respectively), suggesting that a cadmium chloride-induced increase in the fura-2 fluorescence ratio is dependent on an increase in intracellular heavy metal cations but not intracellular Ca2+[1]. TPEN is a metal chelator, which targets colon cancer cells through redox cycling of copper. TPEN reduces cell viability in a dose- and time-dependent manner. TPEN-induced cell death is 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[2].

[Cell Assay]

Human neuroblastoma cell line SH-SY5Y, are grown in Dulbecco’s Modified Eagle’s Medium (DMEM) mixed 1:1 with Ham’s F-12 nutrient mixture containing 10% fetal bovine serum, 100 unit/mL penicillin and 100 μg/mL streptomycin at 37°C in a humidified 5% CO2 atmosphere. Two days before experimentation, cells are seeded at a density of 7×104 cells/cm2 in a 96-well plate. Cells in a 96-well plate are serum-starved for 4 hr; calcium indicator fura-2 is then loaded into the cells by using Calcium kit II fura-2. In brief, SH-SY5Ycells are incubated with 5 μM fura-2/AM in the presence of 0.04% Pluronic F-127, a dispersing agent to improve the efficiency of loading with fura-2, and 1.25 mM probenecid, a blocker of organic anion transport to prevent leakage of fura-2 from cells. After 1 hr incubation at 37°C, fura-2 fluorescence is measured at 500 nm emission after excitation at 340 nm (F340) or 380 nm (F380) using an Infinite M200 plate reader at 37°C.The change in [Ca2+]i is reflected by the ratio of F340 and F380. To determine the changes in fura-2 fluorescence ratio induced by heavy metal compounds, cells are treated with manganese chloride, lead acetate, cadmium chloride , mercuric chloride and MeHg chloride dissolved in distilled water. We confirmed that the cells adhered to the bottom of the plate after 6 hr exposure to heavy metal compounds. The cells are also treated with three Ca2+ channel blockers, lanthanum chloride dissolved in distilled water, verapamil and 2-APB dissolved in DMSO, 30 min before heavy metal exposure. The heavy metal chelator TPEN is dissolved in DMSO and added 3 hr after the stimulation with heavy metals to determine the contribution of endogenous and exogenous heavy metals on fura-2 fluorescence changes. We measured the effect of TPEN (20 μM) on the fura-2 fluorescence ratio after a 10 min treatment with TPEN, since our preliminary experiments showed that the effect of TPEN on fura-2 fluorescence reached maximum and stabilized within 10 min of the treatment[1].

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
542.1±45.0 °C at 760 mmHg

[ Melting Point ]:
110-112 °C

[ Molecular Formula ]:
C₂₆H₂₈N₆

[ Molecular Weight ]:
424.541

[ Flash Point ]:
281.7±28.7 °C

[ Exact Mass ]:
424.237549

[ PSA ]:
58.04000

[ LogP ]:
2.68

[ Vapour Pressure ]:
0.0±1.4 mmHg at 25°C

[ Index of Refraction ]:
1.632

[ Storage condition ]:
Refrigerator

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2933399090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933399090

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Redistribution of subcellular calcium and its effect on apoptosis in primary cultures of rat proximal tubular cells exposed to lead.

Toxicology 333 , 137-46, (2015)

Previous studies have shown that cytosolic Ca(2+) ([Ca(2+)]c) overload was involved in Pb-induced apoptosis in primary cultures of rat proximal tubular (rPT) cells, but the source of elevated Ca(2+) a...

Rat pancreatitis produced by 13-week administration of zinc oxide nanoparticles: biopersistence of nanoparticles and possible solutions.

J. Appl. Toxicol. 33(10) , 1089-96, (2013)

Zinc oxide (ZnO) nanoparticles (NPs) are used in diverse applications ranging from paints and cosmetics to biomedicine and food. Although micron-sized ZnO is a traditional food supplement, ZnO NPs are...

Zinc is released by cultured astrocytes as a gliotransmitter under hypoosmotic stress-loaded conditions and regulates microglial activity.

Life Sci. 94(2) , 137-44, (2014)

Astrocytes contribute to the maintenance of brain homeostasis via the release of gliotransmitters such as ATP and glutamate. Here we examined whether zinc was released from astrocytes under stress-loa...

Related Compounds

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