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
Bone morphogenetic proteins (BMPs), members of the TGFβ superfamily, play an important role in stem cell biology and function to regulate cell proliferation and differentiation during development. 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]. K02288 is a potent BMP type I receptor inhibitor with IC50s of 1.8, 1.1, 6.4 nM for ALK1, ALK2 and ALK6, respectively. K02288 also shows slightly weaker inhibition against ALK3 and ALK6 with IC50s of of 5-34 nM. Furthermore, K02288 further demonstrated an improved selectivity against ALK4 and ALK5 with IC50s of 321 nM and 302 nM, respectively. In C2C12 cells, the phosphorylation of Smad1/5/8, induced by BMP4, can be reduced by K02288 in a dose dependent manner with an apparent IC50 of 100 nM [4]. In LX-2 cells, the proliferation promotion effect of BMP9 stimulation was inhibited by incubating with 1μM of K02288 for 4 hours. In addition, the expression of pSMAD1/5, ID1, and α-SMA were significantly decreased by K02288 treatment[5]. On embryo development day 6, 100μl of K02288 (1μM) was deposited on the chick embryo chorioallantoic membrane (CAM) model. Four days later, a large fraction of the CAM models exhibited a distinctive phenotype of low vessel density reflecting the dysfunctional angiogenesis which occurs following hypersprouting[1].
作用机制
K02288 binds type I BMP receptor at the ATP-binding pocket. The 2-aminopyridine group of K02288 is an ATP-mimetic that binds the kinase hinge region of type I BMP receptor through two conserved hydrogen bonds[4].
K02288 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Huh7 cells
0.25 µM
5 days
Suppressed not only ID1 and EpCAM expression
Mol Oncol. 2021 Aug;15(8):2203-2218.
MT cells
0.25 µM
5 days
Suppressed not only ID1 and EpCAM expression
Mol Oncol. 2021 Aug;15(8):2203-2218.
Huh7 cells
1 µM
24 hours
Suppressed the cell invasion/migration ability
Mol Oncol. 2021 Aug;15(8):2203-2218.
MT cells
1 µM
24 hours
Suppressed the cell invasion/migration ability
Mol Oncol. 2021 Aug;15(8):2203-2218.
Lgr5+ CSCs
6.4 nM
3, 5, 7 days
K02288 attenuated the radiosensitizing effect of PD on Lgr5+ CSCs, indicating that PD regulates the radiosensitivity of CSCs through the BMP signaling pathway
Int J Biol Sci. 2019 Jan 1;15(2):430-440.
Human Umbilical Vein Endothelial Cells (HUVECs)
1 µM
30 minutes
K02288 inhibited BMP9-induced phosphorylation of SMAD1/5/8, reducing both the SMAD and Notch-dependent transcriptional responses.
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