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 bone morphogenetic protein (BMP) signaling pathway has essential functions in development, homeostasis, and in the normal and pathophysiologic remodeling of tissues. BMPs initiate their signaling events through an interaction of their type I and type II receptors, both of which are transmembrane serine/threonine kinases. Seven type I receptors (a.k.a. activin receptor-like receptors; ALK1 to ALK7) and four type II receptors have been identified in mice and humans[3].. LDN-212854 is a selective and potent inhibitor of the BMP type I receptor kinases, with the IC50 values of 1.3 nM, 2.4 nM, 85.8 nM, 2133 nM, 9276 nM for ALK2, ALK1, ALK3, ALK4 and ALK5, respectively. LDN-212854 (IC50=37 nM) displayed low nanomolar potency in blocking the phosphorylation of SMAD1/5/8 induced by BMP7 (20 ng/mL, 30 min) in BMPR2−/− pulmonary vascular smooth muscle cells. ALK2Q207D transgenic mice model was used to evaluate the efficacy of LDN-212854 in vivo. After pretreating pericytes with 570nM LDN-212854 for 1 day, the osteoblast differentiation of pericytes from FOR hiPSCs was partly inhibited. Treatment with LDN-212854 on the dose of 6 mg/kg twice daily for 4 weeks can prevent the formation of heterotopic bone and preserved limb range of motion with minimal or no impairment in the majority of mice[4].
作用机制
LDN-212854 binds type I BMP receptor at the ATP-binding pocket. The pendant 5-quinoline group of LDN-212854 is predicted to form an alternative water-mediated hydrogen bond to the catalytic lysine (K235) of ALK2[5].
LDN-212854 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mesenchymal cells
750 nM
12, 24, 48, 72, and 96 hr
Evaluate the effect of LDN-212854 on mesenchymal cell proliferation, results show LDN-212854 significantly reduces cell proliferation
To evaluate the effect of LDN-212854 on OPC differentiation in the presence of fibrinogen, results showed that LDN-212854 restored mature oligodendrocyte differentiation and reduced GFAP+ astrocyte formation.
Brain. 2021 Sep 4;144(8):2291-2301.
HSG cells
0.1, 1.0 or 10 nM
4 days
To investigate the effect of LDN-212854 on BMP6-induced loss of cell membrane water permeability. Results showed that LDN-212854 inhibited BMP6-induced RVD loss in a dose-dependent manner.
Sci Rep. 2020 Feb 19;10(1):2967.
HSG cells
10 or 60 nM
24 hours
To investigate the effect of LDN-212854 on BMP6-induced SMAD1/5/8 phosphorylation. Results showed that 60 nM LDN-212854 significantly reduced BMP6-induced SMAD1/5/8 phosphorylation.
Sci Rep. 2020 Feb 19;10(1):2967.
C2C12 cells
500 nM
3 days
To test the inhibitory effect of LDN-212854 on BMP2-induced alkaline phosphatase (ALP) activity, results showed that LDN-212854 significantly suppressed ALP activity.
Stem Cell Res Ther. 2024 Apr 5;15(1):98.
Human mesenchymal stromal cells (MSCs)
500 nM
28 days
To test the effect of LDN-212854 on MSC chondrogenesis in vitro, results showed that LDN-212854 mildly inhibited chondrogenesis but had limited effects on hypertrophy markers.
Stem Cell Res Ther. 2024 Apr 5;15(1):98.
LDN-212854 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Ntv-a;p53fl/fl mice
Intraperitoneally
6 mg/kg
Twice daily for 5 consecutive days (in vitro); twice a day until euthanasia endpoints were met (in vivo survival study)
To evaluate the effect of LDN212854 on tumor growth and survival, results showed that LDN212854 significantly prolonged survival.
Nat Commun. 2019 Mar 4;10(1):1023.
Mice
Burn/tenotomy model
Intraperitoneal injection
6 mg/kg
Daily for 6 weeks
Evaluate the effect of LDN-212854 on trauma-induced heterotopic ossification, results show LDN-212854 significantly reduces heterotopic ossification volume
Mol Ther. 2017 Aug 2;25(8):1974-1987.
Mouse
Acvr1[R206H]FlEx/+ conditional knock-in mice
Subcutaneous injection
3 mg/kg
Twice daily for 4 weeks
LDN-212854 effectively suppressed spontaneous joint/ligament HO and injury-triggered intramuscular HO in Acvr1R206H mice, demonstrating selective ACVR1 inhibition abrogates cell-autonomous effects of mutant receptors in tendon and muscle progenitors.
Sci Transl Med. 2016 Nov 23;8(366):366ra163
Mice
C57BL/6.NOD-Aec1Aec2 mouse model
Intraperitoneal injection
2.5 mg/kg
Once daily for 24 days
To investigate the effect of LDN-212854 on the restoration of salivary gland function in C57BL/6.NOD-Aec1Aec2 mice. Results showed that LDN-212854 treatment significantly increased salivary flow rate and reduced phosphorylation of SMAD1/5/8 and expression of ID3.
Sci Rep. 2020 Feb 19;10(1):2967.
NCG mice
HCC xenograft model
Intraperitoneal injection
6 mg/kg
Twice daily for 10-14 days
LDN-212854 significantly suppressed HCC tumor growth and induced global RNA m6A methylation
搜索
HazMat Fee +
