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 transforming growth factor (TGF)-β superfamily has been implicated into different physiological and pathological processes in a broad range of cell systems. The TGF-β receptor complex is composed of type I, type II and accessory receptors. TGF-β type I receptors have seven isoforms termed activin receptor-like kinases (ALKs) 1 - 7[2]. ML347 is a selective inhibitor of ALK1/2/3/6 with IC50 values of 46 nM, 32 nM, 10.8 μM and 9.83 μM, respectively[1]. In vitro, ML347 at dose of 50 nM dampened the GDF2-induced SMAD1/5 phosphorylation in MCF10A cells that express high levels of ALK2[3]. Utilizing rapid equilibrium dialysis, the protein binding of ML347 was determined in human, rat and mouse plasma shown that similar in all three species with ML347 displaying high plasma protein biding (Fu~0.01 - 0.015). ML347 was unstable to oxidative metabolism – possibly due to the labile methoxy group and therefore was predicted to display high clearance in human and mouse, and moderate to-high clearance in the rat[1].
ML347 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT15
25 µM
To evaluate the effect of ML347 on HCT15 cells
BMC Med. 2023 Sep 25;21(1):366.
HUVECs
0.5 or 1 µM
12 h
To evaluate the inhibitory effect of ML347 on Dkk-3-mediated VEGF upregulation. The results showed that ML347 exposure abrogated the VEGF upregulation induced by hrDkk-3.
Front Pharmacol. 2017 Mar 14;8:111.
HUVECs
0.5 or 1 µM
12 h
To evaluate the inhibitory effect of ML347 on Dkk-3-mediated VEGF upregulation. The results showed that ML347 exposure abrogated the VEGF upregulation induced by hrDkk-3.
Front Pharmacol. 2017 Mar 14;8:111.
C2C12BRA cells
152 nM
Evaluate the activity of ML347 in the BMP4 cell assay, showing an IC50 of 152 nM
Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.
ML347 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Chronic constriction injury (CCI) model
Intrathecal injection
100 ng
Single injection
ML347, as an ALK1 selective inhibitor, was used to determine whether the effects of SIN on CCI mice were mediated through the ALK1 receptor. The results showed that ML347 did not reverse the analgesic effects of SIN, indicating that ALK1 is not involved in the action of SIN.
J Cell Mol Med. 2024 Nov;28(22):e70214
B-NSG mice
Patient-derived xenograft (PDX) model
Intraperitoneal injection
45 mg/kg
Every other day for 3 weeks
To evaluate the effect of ML347 in combination with Regorafenib on tumor growth, results showed that the combination therapy significantly inhibited tumor growth
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