K02288

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Chemical Structure| 1431985-92-0 同义名 : -
CAS号 : 1431985-92-0
货号 : A151373
分子式 : C20H20N2O4
纯度 : 99%+
分子量 : 352.384
MDL号 : MFCD26936347
存储条件：

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 55 mg/mL(156.08 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • ALK1

    ALK1, IC50:1.8 nM

  • ALK2

    ALK2, IC50:1.1 nM

  • ALK6

    ALK6, IC50:6.4 nM

  • ALK3

    ALK3, IC50:34.4 nM
描述 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].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK293T cells Function assay 30 mins Inhibition of TGFbeta1-induced TGFbeta type 1 ALK5 in HEK293T cells after 30 mins by luciferase reporter gene assay, IC50=3.4 μM 25101911
mouse C2C12 cells Function assay 30 mins Inhibition of BMP2-induced BMP receptor type 1 ALK2 in mouse C2C12 cells after 30 mins by luciferase reporter gene assay, IC50=0.23 μM 25101911
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.84mL

0.57mL

0.28mL

14.19mL

2.84mL

1.42mL

28.38mL

5.68mL

2.84mL
参考文献

[1]Kerr G, Sheldon H, Chaikuad A, Alfano I, von Delft F, Bullock AN, Harris AL. A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis. Angiogenesis. 2015 Apr;18(2):209-17

[2]Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN. A new class of small molecule inhibitor of BMP signaling. PLoS One. 2013 Apr 30;8(4):e62721.

[3]Luo J, Tang M, Huang J, He BC, Gao JL, Chen L, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Bi Y, Luo X, Jiang W, Su Y, Shen J, Kim SH, Huang E, Gao Y, Zhou JZ, Yang K, Luu HH, Pan X, Haydon RC, Deng ZL, He TC. TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells. J Biol Chem. 2010 Sep 17;285(38):29588-98

[4]Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN. A new class of small molecule inhibitor of BMP signaling. PLoS One. 2013 Apr 30;8(4):e6272

[5]Li P, Li Y, Zhu L, Yang Z, He J, Wang L, Shang Q, Pan H, Wang H, Ma X, Li B, Fan X, Ge S, Jia R, Zhang H. Targeting secreted cytokine BMP9 gates the attenuation of hepatic fibrosis. Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):709-720.