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Dp44mT is an iron chelator with selective anticancer activity. Dp44mT alone induced selective cell killing in the breast cancer cell line MDA-MB-231, due to selective inhibition of top2alpha, when compared with healthy mammary epithelial cells (MCF-12A). It induces G1 cell cycle arrest and reduces cancer cell clonogenic growth at nanomolar concentrations. Dp44mT, but not the iron chelator desferal, induces DNA double-strand breaks quantified as S139 phosphorylated histone foci (gamma-H2AX) and Comet tails induced in MDA-MB-231 cells. Doxorubicin-induced cytotoxicity and DNA damage were both enhanced significantly in the presence of low concentrations of Dp44mT. The chelator caused selective poisoning of DNA topoisomerase IIalpha (top2alpha) as measured by an in vitro DNA cleavage assay and cellular topoisomerase-DNA complex formation[3]. Dp44mT targets lysosome integrity through copper binding. Copper binding is essential for the potent antitumor activity of Dp44mT, as coincubation with nontoxic copper chelators markedly attenuated its cytotoxicity[4]. Dp44mT induces translocation of TFEB to the nucleus and it was AMPK-dependent[5].
Dp44mT 细胞实验
Cell Line
Concentration
Treated Time
Description
References
RD rhabdomyosarcoma cells
7.2 nM
72 hours
Evaluated the antiproliferative effect of Dp44mT, showing significant inhibition on RD cells
Front Pharmacol. 2022 Sep 7;13:976955
Saos-2 osteosarcoma cells
15.3 nM
72 hours
Evaluated the antiproliferative effect of Dp44mT, showing significant inhibition on Saos-2 cells
Front Pharmacol. 2022 Sep 7;13:976955
DAOY medulloblastoma cells
11.1 nM
72 hours
Evaluated the antiproliferative effect of Dp44mT, showing significant inhibition on DAOY cells
Front Pharmacol. 2022 Sep 7;13:976955
SK-N-BE(2) neuroblastoma cells
2.3 nM
72 hours
Evaluated the antiproliferative effect of Dp44mT, showing significant inhibition on SK-N-BE(2) cells
Front Pharmacol. 2022 Sep 7;13:976955
SH-SY5Y neuroblastoma cells
1.1 nM
72 hours
Evaluated the antiproliferative effect of Dp44mT, showing significant inhibition on SH-SY5Y cells
Front Pharmacol. 2022 Sep 7;13:976955
RD rhabdomyosarcoma cells
9.4 μM
24 h
To evaluate the synergistic effect of Dp44mT with anthracyclines, showing synergistic effects
Int J Mol Sci. 2022 Aug 1;23(15):8549
Daoy medulloblastoma cells
7.9 μM
24 h
To evaluate the synergistic effect of Dp44mT with anthracyclines, showing synergistic effects
Int J Mol Sci. 2022 Aug 1;23(15):8549
Saos-2 osteosarcoma cells
6.6 μM
24 h
To evaluate the synergistic effect of Dp44mT with anthracyclines, showing moderate antagonism
Int J Mol Sci. 2022 Aug 1;23(15):8549
SK-N-BE(2) neuroblastoma cells
4.2 μM
24 h
To evaluate the synergistic effect of Dp44mT with anthracyclines, showing synergistic effects
Int J Mol Sci. 2022 Aug 1;23(15):8549
SH-SY5Y neuroblastoma cells
1.9 μM
24 h
To evaluate the synergistic effect of Dp44mT with anthracyclines, showing synergistic effects
Int J Mol Sci. 2022 Aug 1;23(15):8549
SH-SY5Y
25 μM
24 hours
To evaluate the apoptosis-inducing effect of Dp44mT on non-MYCN-amplified neuroblastoma cells, results showed that Dp44mT significantly increased early and late apoptosis in SH-SY5Y cells.
J Hematol Oncol. 2016 Sep 27;9(1):98
SK-N-AS
25 μM
24 hours
To evaluate the apoptosis-inducing effect of Dp44mT on non-MYCN-amplified neuroblastoma cells, results showed that Dp44mT significantly increased early and late apoptosis in SK-N-AS cells.
J Hematol Oncol. 2016 Sep 27;9(1):98
BE(2)C
25 μM
24 hours
To evaluate the apoptosis-inducing effect of Dp44mT on MYCN-amplified neuroblastoma cells, results showed that Dp44mT significantly increased early and late apoptosis in BE(2)C cells.
J Hematol Oncol. 2016 Sep 27;9(1):98
SK-N-LP
25 μM
24 hours
To evaluate the anti-proliferative activity of Dp44mT on neuroblastoma cells, results showed that Dp44mT significantly inhibited the proliferation of SK-N-LP cells.
J Hematol Oncol. 2016 Sep 27;9(1):98
HCT-15 cells
0.1–10μM
24 hours
To evaluate the cytotoxicity of Dp44mT on colon cancer cells and its effect on Pgp protein levels. Results showed Dp44mT had significant cytotoxicity on HCT-15 cells.
Cell Death Dis. 2016 Dec 1;7(12):e2510
MDA-MB-231 cells
0.1–10μM
24 hours
To evaluate the cytotoxicity of Dp44mT on breast cancer cells and its effect on Pgp protein levels. Results showed Dp44mT had significant cytotoxicity on MDA-MB-231 cells.
Cell Death Dis. 2016 Dec 1;7(12):e2510
MCF7 cells
0.1–10μM
24 hours
To evaluate the cytotoxicity of Dp44mT on breast cancer cells and its effect on Pgp protein levels. Results showed Dp44mT had significant cytotoxicity on MCF7 cells.
Cell Death Dis. 2016 Dec 1;7(12):e2510
KB31 cells
0.1–10μM
24 hours
To evaluate the cytotoxicity of Dp44mT on low Pgp-expressing cells and its effect on Pgp protein levels. Results showed Dp44mT had lower cytotoxicity on KB31 cells.
Cell Death Dis. 2016 Dec 1;7(12):e2510
KBV1 cells
0.1–10μM
24 hours
To evaluate the cytotoxicity of Dp44mT on Pgp-expressing cells and its effect on Pgp protein levels. Results showed Dp44mT significantly decreased Pgp expression and selectively killed Pgp-expressing cells.
Cell Death Dis. 2016 Dec 1;7(12):e2510
MDA-MB-157 breast cancer cells
5 μM
48-72 hours
Induced cytoplasmic vacuolation and lipid droplet accumulation, consistent with MDA-MB-231 phenotype
J Exp Clin Cancer Res. 2018 Apr 3;37(1):75
MDA-MB-231 breast cancer cells
5 μM
48-72 hours
Induced cytoplasmic vacuolation and lipid droplet accumulation, leading to non-apoptotic cell death
J Exp Clin Cancer Res. 2018 Apr 3;37(1):75
OECM-1 cells
0-20 µM
24 hours
Dp44mT significantly inhibited OECM-1 cell growth and upregulated NDRG1 and NDRG3 protein expressions.
Int J Mol Sci. 2016 Aug 31;17(9):1435
SAS cells
0-20 µM
24 hours
Dp44mT significantly inhibited SAS cell growth, partly due to induction of G1 cell cycle arrest.
Int J Mol Sci. 2016 Aug 31;17(9):1435
Dp44mT 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Xenograft model
Intravenous injection
0.5 mg/kg
Once daily for 17 days
Dp44mT significantly inhibited tumor growth of SAS cells in vivo without affecting body weight of mice.
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