LDN-214117

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Chemical Structure| 1627503-67-6 同义名 : -
CAS号 : 1627503-67-6
货号 : A637146
分子式 : C25H29N3O3
纯度 : 98%
分子量 : 419.516
MDL号 : MFCD28168043
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: 18 mg/mL(42.91 mM)，配合低频超声，并水浴加热至45℃助溶，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：

2% DMSO+30% PEG 300+2% Tween 80+water 3 mg/mL

生物活性
靶点

  • ALK2

    ALK2, IC50:24 nM
描述 The bone morphogenetic protein (BMP) signal transduction pathway is a subset of the larger TGF-β signaling family, which includes 7 type I receptors, 5 type II receptors, and over 30 ligands of the BMP, TGF-β, activin, and growth and differentiation factor (GDF) ligand families[2]. LDN-214117 is a high degree of selectivity inhibitor for the BMP type I receptor kinase ALK2 with IC50 value of 24 nM. LDN-214117 also inhibits the activity of BMP6 and TGFβ with IC50 values of 67 nM and 14.65 μM, respectively (measured by ligand induced transcriptional assay)[1]. In vitro, LDN-214117 inhibited ACR1 wild-type cells SU-DIPG-VI and QCTB-R059 with GI50 values of 5.38 μM and 8.27 μM, respectively. LDN-214117 also inhibited cell viability of the ACVR1 mutant cells HSJD-DIPG-007(R206H), SU-DIPG-IV(G238V) and HSJD-DIPG-018(R258G) with GI50 values of 1.57 μM, 6.23 μM and 16.38 μM, respectively. Treatment DIPG cell lines SU-DIPG-VI and HSJD-DIPG-IV with 0.1 μM LDN-214117 for 4h inhibited phosphor-SMAD1/5/8 and the downstream effector ID1[3]. In addition, treatment the lung carcinoma cell line LCLC-103H with LDN-214117 at concentration of 5 μM significantly hindered the migration of LCLC-103H cells into the wound area, reaching relative wound density of only 50% in 48h by inhibition of BMP signaling[4]. In vivo, the bioavailability (F) and well-tolerance level of LDN-214117 was 0.75 and 25 mg/kg, respectively. Oral administration of LD-214117 at 25 mg/kg for 28 days extended survival in immunodeprived mice bearing orthotopic xenografts of H3.3K27M, ACVR1R206H mutant HSJDDIPG-007 cells[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
C2C12 cells Function assay 30 mins Inhibition of BMP6-induced BMP receptor type 1 ALK2 in mouse C2C12 cells after 30 mins by luciferase reporter gene assay, IC50=0.1 μM 25101911
HEK293T cells Function assay 30 mins Inhibition of ALK1 (unknown origin) expressed in HEK293T cells after 30 mins by luciferase reporter gene assay, IC50=0.027 μM 25101911
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.38mL

0.48mL

0.24mL

11.92mL

2.38mL

1.19mL

23.84mL

4.77mL

2.38mL
参考文献

[1]Mohedas A H , Wang Y , Sanvitale C E , et al. Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. Journal of Medicinal Chemistry, 2014, 57(19).

[2]Dinter T, Bocobo G, Yu P B, et al. Pharmacologic Strategies for Assaying BMP Signaling Function. Methods of Molecular Biology, 2019: 221-233.

[3]Carvalho D, Taylor KR, Olaciregui NG, et al. ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma. Commun Biol. 2019;2:156.

[4]Mihajlovic J, Diehl L A, Hochhaus A, et al. Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells. Journal of Cancer Research and Clinical Oncology, 2019, 145(11): 2675-2687.