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LDN-214117
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
LDN-214117图片
CAS NO:1627503-67-6
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
LDN-214117 (LDN 214117; LDN214117) is a novel, potent and selective ALK2 (BMP type I receptor kinase) inhibitor with potential anticancer activity. It inhibits ALK2 with an IC50 of 24 nM.
理化性质和储存条件
Molecular Weight (MW)419.52
FormulaC25H29N3O3
CAS No.1627503-67-6
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 83 mg/mL (197.8 mM)
Water: <1 mg/mL
Ethanol: 83 mg/mL (197.8 mM)
Other info
Chemical Name: 1-(4-(6-methyl-5-(3,4,5-trimethoxyphenyl)pyridin-3-yl)phenyl)piperazine
InChi Key: BHUXVRVMMYAXKN-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H29N3O3/c1-17-22(19-14-23(29-2)25(31-4)24(15-19)30-3)13-20(16-27-17)18-5-7-21(8-6-18)28-11-9-26-10-12-28/h5-8,13-16,26H,9-12H2,1-4H3
SMILES Code: COC1=C(OC)C(OC)=CC(C2=C(C)N=CC(C3=CC=C(N4CCNCC4)C=C3)=C2)=C1
SynonymsLDN214117; LDN 214117; LDN-214117
实验参考方法
In Vitro

In vitro activity: The kinase most highly inhibited by LDN-214117 is ALK2 (IC50, 24 nM), followed by TNIK, RIPK2, and ABL1. LDN-214117 demonstrates selective inhibition of ALK2 and ALK1 in preference to ALK3 kinase activity. LDN-214117 exhibits relatively selective inhibition of BMP6 versus BMP2 or BMP4. In a cell-based assay, LDN-214117 exhibits a selective inhibition on BMP6 with IC50 of approximately 100 nM, and 164-fold selectivity for BMP6 versus TGF-β1.


Kinase Assay: Purified recombinant ALK2 proteins, ATP, ATP[γ-32P], and dephosphorylated casein at final concentrations of 2.5 nM, 6 μM, 0.05 μCi/μL , and 0.5 mg/mL, respectively, are aliquoted in kinase buffer containing 0.2% BSA supplemented with 10 mM MnCl2 into 96-microwell plates, in combination with inhibitor compounds diluted at varying concentrations (0.01 nM to 100 μM). Positive control samples lacking inhibitor compounds, and negative controls lacking recombinant kinase, are also measured. The mixture is reacted at RT for 45 min, quenched with a final concentration of 2% phosphoric acid. The reaction mixture is transferred to 96-well P81 phosphocellulose filter plates and bound for 5 min. The plates are washed 20 times with 150 μL of 1% phosphoric acid solution per well by vacuum manifold. Plates are dried at RT for 1 h, sealed, and assayed with Microscint 20 scintillation fluid using a Spectramax L luminometer. Data is normalized to positive controls at 100% enzyme activity, with negative controls being subtracted as background.


Cell Assay: Cells are seeded at 25000 cells per well in 96-well plates and incubated for 2 h at 37℃ and 5% CO2. Compounds of LDN-214117 or DMSO are diluted in DMEM and added at final compound concentrations of 1, 10, and 100 μM. Cells are incubated for 4 and 24 h, after which the media is discarded. Cells are lysed by adding 30 μL of passive lysis buffer and shaken at RT for 15 min. Cell viability is determined by quantifying the ATP present in each well by adding 10 μL of Cell Titer Glo per well and measuring the light output by Spectramax L luminometer. Data is normalized to 100% viability for cells receiving only DMSO.

In Vivo
Animal model
Formulation & Dosage
References

J Med Chem. 2014 Oct 9;57(19):7900-15.