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Zinc Pyrithione is an antifungal and antibacterial agent by disrupting membrane transport through blocking the proton pump[1]. Zinc Pyrithione is also a copper ionophore, facilitating the transport of copper ions into cells, which is beneficial for studying cuproptosis[2].
体外研究
Zinc Pyrithione is a coordination complex where the pyrithione ligands, formally monoanions, chelate to zinc ions (Zn 2+) via oxygen and sulfur centers. In its crystalline form, it forms a centrosymmetric dimer, with each zinc ion bonded to two sulfur and three oxygen centers. In solution, these dimers can dissociate by breaking one Zn-O bond. As a dimer, Zinc Pyrithione is likely biologically active in its monomer form and is known to induce plasma membrane depolarization, with a half-maximal effective concentration (K1/2) of approximately 0.3 mM[1].
Zinc Pyrithione, at concentrations ranging from 10 nM to 10 μM over a period of 72 hours, significantly promotes cell death in AAVS1 cells[2].
Zinc pyrithione/吡啶硫酮锌 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human lung tissue (HLT) cells
30, 10, 1, 0.5 µM
1 hour
Evaluation of zinc pyrithione's inhibitory effect on SARS-CoV-2 entry, showing 93.12% inhibition at 30 μM concentration.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2158-2168.
DRG neurons
1 µM
20 seconds
ZnPy induces Ca2+ responses via TRPA1
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8374-9.
Evaluate the synergistic antibacterial effect of zinc pyrithione with gentamicin, showing strong synergy
Antibiotics (Basel). 2022 Jul 17;11(7):960.
Streptococcus agalactiae
0.031 µg/mL
24 hours
Evaluate the synergistic antibacterial effect of zinc pyrithione with gentamicin, showing strong synergy
Antibiotics (Basel). 2022 Jul 17;11(7):960.
Staphylococcus aureus
0.25 µg/mL
24 hours
Evaluate the synergistic antibacterial effect of zinc pyrithione with gentamicin, showing high susceptibility in some strains
Antibiotics (Basel). 2022 Jul 17;11(7):960.
HSC2 cells
0.5 µM to 2 µM
48 hours
PYZ treatment led to 52.7% cells in sub-G0 phase and significantly increased apoptosis (from 21.6% to 88.8%).
Mol Oncol. 2015 Oct;9(8):1720-35.
MDA1986 cells
0.5 µM to 2 µM
48 hours
PYZ treatment resulted in 85.7% cells in sub-G0 phase and markedly induced apoptosis (increased from 16.9% to 93.6%).
Mol Oncol. 2015 Oct;9(8):1720-35.
SCC4 cells
0.5 µM to 2 µM
48 hours
PYZ treatment induced cell cycle arrest and apoptosis, significantly increasing sub-G0 fraction (65.6%) and activating cleavage of caspase 3, caspase 9, and PARP.
Mol Oncol. 2015 Oct;9(8):1720-35.
M10 cells
0.5 µM
72 hours
To evaluate the effect of zinc pyrithione on the proliferation, intracellular free zinc content, and autophagic activity of M10 cells. Results showed that 0.5 µM zinc pyrithione significantly increased intracellular free zinc levels, inhibited cell proliferation, and enhanced autophagic activity over 72 hours.
Int J Mol Sci. 2021 Jan 11;22(2):667.
M9 cells
0.5 µM
72 hours
To evaluate the effect of zinc pyrithione on the proliferation, intracellular free zinc content, and autophagic activity of M9 cells. Results showed that 0.5 µM zinc pyrithione significantly increased intracellular free zinc levels, strongly inhibited cell proliferation, and significantly enhanced autophagic activity over 72 hours.
Int J Mol Sci. 2021 Jan 11;22(2):667.
M5 cells
0.5 µM
72 hours
To evaluate the effect of zinc pyrithione on the proliferation, intracellular free zinc content, and autophagic activity of M5 cells. Results showed that 0.5 µM zinc pyrithione significantly increased intracellular free zinc levels, inhibited cell proliferation, and enhanced autophagic activity over 72 hours.
Int J Mol Sci. 2021 Jan 11;22(2):667.
HEM cells
0.5 µM
72 hours
To evaluate the effect of zinc pyrithione on the proliferation and intracellular free zinc content of HEM cells. Results showed that 0.5 µM zinc pyrithione significantly increased intracellular free zinc levels but had a weaker inhibitory effect on cell proliferation over 72 hours.
Int J Mol Sci. 2021 Jan 11;22(2):667.
Bowes cells
0.5 µM
72 hours
To evaluate the effect of zinc pyrithione on the proliferation and intracellular free zinc content of Bowes cells. Results showed that 0.5 µM zinc pyrithione significantly increased intracellular free zinc levels and inhibited cell proliferation over 72 hours.
Int J Mol Sci. 2021 Jan 11;22(2):667.
FHs 74 Int (normal intestinal cells)
0.3 µg/mL
72 hours
Evaluate the cytotoxicity of zinc pyrithione on normal intestinal cells, showing some toxicity to normal cells.
Pharmaceuticals (Basel). 2020 Sep 3;13(9):233.
Caco-2 (intestinal cancer cells)
0.7 µg/mL
72 hours
Evaluate the antiproliferative activity of zinc pyrithione on Caco-2 intestinal cancer cells, showing significant cytotoxicity.
Pharmaceuticals (Basel). 2020 Sep 3;13(9):233.
HT29 (intestinal cancer cells)
0.6 µg/mL
72 hours
Evaluate the antiproliferative activity of zinc pyrithione on HT29 intestinal cancer cells, showing significant cytotoxicity.
Pharmaceuticals (Basel). 2020 Sep 3;13(9):233.
CHO cells
2.4 µM (EC50)
ZnPy activates TRPA1 by increasing intracellular Zn2+ concentration
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8374-9.
CHO cells
10 µM
Study the effect of ZnPy on KCNQ3 channels, showing no response to ZnPy.
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3128-33.
CHO cells
10 µM
Investigate the potentiating effect of ZnPy on KCNQ2 channels, showing significant increase in current amplitude.
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3128-33.
Hippocampal neurons
10 µM
To study the inhibitory effect of ZnPy on neuronal firing after muscarinic receptor activation. Results showed that ZnPy completely abolished Oxo-M-induced spontaneous firing, whereas retigabine only partially inhibited it.
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8726-31.
CHO cells
10 µM
To investigate the augmentation effect of ZnPy on KCNQ2 currents after M1 receptor activation. Results showed that ZnPy immediately augmented the Oxo-M suppressed KCNQ2 current, and the effect was reversible.
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8726-31.
Zinc pyrithione/吡啶硫酮锌 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NOD/SCID/Crl mice
SCC4 xenograft model
Intraperitoneal injection
1 mg/kg
Weekly for 6 weeks
PYZ treatment significantly reduced tumor volume (mean 316.24 mm3 vs control 479.6 mm3) without apparent toxicity. β-catenin expression decreased (positive cells reduced from 67% to 8%).
Mol Oncol. 2015 Oct;9(8):1720-35.
Drosophila melanogaster
GNAO1 encephalopathy model
Dietary supplementation
10 µM
Continuous supplementation starting from the egg stage
To test the effect of dietary zinc supplementation on the motor function and lifespan of Drosophila, results showed that ZnCl2 significantly improved the motor function and lifespan of mutant flies.
Sci Adv. 2022 Oct 7;8(40):eabn9350
Human skin
Human abdominal skin
Topical application
2% w/v
24 hours
To assess the delivery and dissolution of zinc pyrithione in hair follicles
Pharmaceutics. 2022 May 17;14(5):1076
Mice
TRPA1-deficient mice
Intraplantar injection
2.5 nmoles
Single injection, observed for 4 hours
CQ induces mechanical hyperalgesia and cold hypersensitivity via TRPA1
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8374-9.
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