There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
The TRPML channels (TRPML1, TRPML2, and TRPML3), belonging to the mucolipin TRP subfamily, primary localize to a population of membrane-bonded vesicles along the endocytosis, and exocytosis pathways. Human viruses enter host cells by plasma membrane penetration or by receptor-mediated endocytosis. TRPML2 enhances the infectivity of a number of enveloped viruses by promoting virus vesicular trafficking and escape from endosomal compartment. TRPML2 expression is stimulated by interferon and by several toll like receptor (TLR) activators, suggesting a possible role in the activation of the innate immune response[1]. ML-SA1, as a selective TRPML agonist, inhibits Dengue virus 2 (DENV2) and Zika virus (ZIKV) by promoting lysosomal acidification and protease activity. The IC50 value of ML-SA1 against DENV2 RNA and ZIKV RNA is 8.3 μM and 52.99 μM, respectively. ML-SA1 can be used for the research of broad-spectrum antiviral. ML-SA1 (25 μM; 0~14 hours; A549 cells) possibly affects the entry of DENV2 into host cells. ML-SA1 (0~200 μM; A549 cells) shows that there is no cytotoxicity to the cell line observed, even at concentrations up to 200 μM. ML-SA1 (0~50 μM; A549 cells) significantly suppresses DENV2 at the RNA levels and the IC50 is 8.93 μM. ML-SA1 results in a dose-dependent decrease in ZIKV in A549 cells at both the RNA and protein levels, and the IC50 value of ML-SA1 against ZIKV RNA is 52.99 μM. ML-SA1, as an activator of TRPMLs, appears to be a potent inhibitor of DENV2 and ZIKV in vitro. ML-SA1 can induce autophagy in Huh7 cells or A549 cells[2]. ML-SA1 blocked LDL-induced increases in intraneuronal and secreted levels of Aβ as well as Aβ accumulation in endolysosomes, prevented BACE1 accumulation in endolysosomes, and decreased BACE1 activity levels. LDL downregulated TRPML1 protein levels, and TRPML1 knockdown worsens LDL-induced increases in Aβ Liang Hui,et al..
ML-SA1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
10 μM
ML-SA1 induced significant [Ca2+]cyt increases
Nat Commun. 2012 Mar 13;3:731
human fibroblasts
25 μM
ML-SA1 activated whole-endolysosome currents
Nat Commun. 2012 Mar 13;3:731
CHO cells
20 μM
ML-SA1 induced rapid increases in GCaMP3 fluorescence
Nat Commun. 2012 Mar 13;3:731
HEK293T cells
10 μM
To validate the activation of TRPML1 channels by ML-SA1, results showed that ML-SA1 significantly increased current density.
Nat Commun. 2018 Oct 10;9(1):4192
DT40 cells
25 μM
In ITPR TKO DT40 cells, ML-SA1 response was significantly enhanced, indicating TMBIM6 regulates lysosomal calcium release independently of ITPR
To investigate the selective modulation of retrograde transport of LEs/amphisomes by TRPML1-mediated Ca2+ efflux. Results showed that ML-SA1 treatment significantly decreased the percentage of retrograde LT+ LAMP1 vesicles, increased the proportion of nonmotile vesicles, and increased pause time and frequency.
Sci Adv. 2022 Apr 29;8(17):eabj5716
FIG4 knockout fibroblasts
40 µM
36 hours
ML-SA1 dramatically reduced the proportion of cells with enlarged LAMP1 positive organelles in FIG4 knockout fibroblasts.
Acta Neuropathol Commun. 2020 Oct 15;8(1):165
LITAF knockout fibroblasts
40 µM
36 hours
ML-SA1 reduced the proportion of cells with enlarged LAMP1 compartments in LITAF knockout fibroblasts.
Acta Neuropathol Commun. 2020 Oct 15;8(1):165
Fibroblasts from CMT1C patients (L125P and T115N mutations)
40 µM
36 hours
ML-SA1 was able to rescue the vacuolation phenotype of LITAF knockout, FIG4 knockout and CMT1C patient fibroblasts.
Acta Neuropathol Commun. 2020 Oct 15;8(1):165
mouse podocytes
20 μM
ML-SA1 significantly reduced exosome concentration in the culture medium of podocytes and enhanced lysosome-multivesicular body (MVB) interaction.
Redox Biol. 2021 Jul;43:102013
Primary rat oligodendrocyte precursor cells
20 μM
72 hours
ML-SA1, as a TRPML1 channel agonist, partially rescues darunavir- and saquinavir-induced inhibition of oligodendrocyte differentiation
J Neuroimmune Pharmacol. 2021 Mar;16(1):169-180
ML-SA1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Male BALB/c mice
Single or multiple uranium exposure models
Intraperitoneal injection
400 or 800 μg/kg
Single administration, evaluated after 24 hours
To evaluate the therapeutic effect of ML-SA1 on uranium-induced nephrotoxicity, results showed that ML-SA1 significantly reduced uranium accumulation in the kidney, mitigated renal proximal tubular injury, and increased apical exocytosis of lysosomes.
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