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LDN-212854

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Chemical Structure| 1432597-26-6 同义名 : BMP Inhibitor III
CAS号 : 1432597-26-6
货号 : A189348
分子式 : C25H22N6
纯度 : 99%+
分子量 : 406.482
MDL号 : MFCD28099808
存储条件：

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

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(73.8 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, IC50:2.4 nM

  • TGFβRI/ALK5

    ALK5, IC50:9276 nM

  • ALK2

    ALK2, IC50:1.3 nM

  • ALK3

    ALK3, IC50:85.8 nM

  • ALK4

    ALK4, IC50:2133 nM
描述 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].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
mouse C2C12BRA cells Function assay 14 h Inhibition of BMP4 in mouse C2C12BRA cells after 14 hrs by luciferase reporter gene assay, IC50=0.117 μM 23639540
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.46mL

0.49mL

0.25mL

12.30mL

2.46mL

1.23mL

24.60mL

4.92mL

2.46mL
参考文献

[1]Mohedas AH, Xing X, et al. Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem Biol. 2013;8(6):1291-302.

[2]Williams E, Bullock AN. Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2. Bone. 2017 Sep 12. pii: S8756-3282(17)30340-X.

[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]Cai J, Orlova VV, Cai X, Eekhoff EMW, Zhang K, Pei D, Pan G, Mummery CL, Ten Dijke P. Induced Pluripotent Stem Cells to Model Human Fibrodysplasia Ossificans Progressiva. Stem Cell Reports. 2015 Dec 8;5(6):963-970.

[5]Mohedas AH, Xing X, Armstrong KA, Bullock AN, Cuny GD, Yu PB. Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem Biol. 2013;8(6):1291-302.