LDN193189 Hydrochloride
(Synonyms: LDN 193189 hydrochloride; LDN-193189 hydrochloride) 目录号 : GC14931
LDN193189 Hydrochloride是一种选择性转录活性形态发生蛋白（BMP）I型受体抑制剂，BMP受体家族包括激活素受体样激酶（ALK1、ALK2、ALK3和ALK6）。LDN193189 Hydrochloride抑制ALK2和ALK3的IC50值分别为5nM和30nM。
Cas No.:1062368-62-0
Sample solution is provided at 25 µL, 10mM.
LDN193189 Hydrochloride is a selective inhibitor of the transcriptionally active morphogenetic protein (BMP) type I receptor, a family of BMP receptors that includes activin receptor-like kinases (ALK1, ALK2, ALK3, and ALK6)[1]. LDN193189 Hydrochloride inhibits ALK2 and ALK3 with IC50 values of 5nM and 30nM, respectively[2]. LDN193189 Hydrochloride can induce the transformation of pluripotent stem cells into neural stem/progenitor cell-like cells[3].
In vitro, LDN193189 Hydrochloride (1, 10μM) treated MC3T3-E1 cells for 12h inhibited the phosphorylation of Smad1/5 (regardless of whether co-incubated with BMP-2) without affecting the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) [4]. LDN193189 Hydrochloride (0-5μM) treated C2C12 cells inhibited the activation of Smad1/5/8, p38 and Akt by different BMP family members in a dose-dependent manner [5].
In vivo, oral administration of LDN193189 Hydrochloride (0.1-10mg/kg) to treat inflammatory anemia mice inhibited Smad1/5 phosphorylation and reduced liver Id1 gene expression and hepcidin mRNA levels in a dose- and time-dependent manner [6]. LDN193189 hydrochloride (3mg/kg) was injected intraperitoneally into mice with breast cancer bone metastasis and showed pro-metastatic properties, accelerating osteolytic lesions[7].
References:
[1] Kim M, Choi O, Pyo S, et al. Identification of novel ALK2 inhibitors and their effect on cancer cells[J]. Biochemical and biophysical research communications, 2017, 492(1): 121-127.
[2] Yu P B, Deng D Y, Lai C S, et al. BMP type I receptor inhibition reduces heterotopic ossification[J]. Nature medicine, 2008, 14(12): 1363-1369.
[3] Minato Y, Nakano-Doi A, Maeda S, et al. A Bone Morphogenetic Protein Signaling Inhibitor, LDN193189, converts ischemia-induced multipotent stem cells into neural stem/progenitor cell-like cells[J]. Stem Cells and Development, 2022, 31(23-24): 756-765.
[4] Takeno A, Kanazawa I, Notsu M, et al. Inhibition of adenosine monophosphate-activated protein kinase suppresses bone morphogenetic protein-2-induced mineralization of osteoblasts via Smad-independent mechanisms[J]. Endocrine Journal, 2018, 65(3): 291-298.
[5] Boergermann J H, Kopf J, Yu P B, et al. Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells[J]. The international journal of biochemistry & cell biology, 2010, 42(11): 1802-1807.
[6] Mayeur C, Kolodziej S A, Wang A, et al. Oral administration of a Bone Morphogenetic Protein (BMP) type I receptor inhibitor prevents the development of anemia of inflammation[J]. 2014.
[7] Vollaire J, Machuca-Gayet I, Lavaud J, et al. The bone morphogenetic protein signaling inhibitor LDN-193189 enhances metastasis development in mice[J]. Frontiers in Pharmacology, 2019, 10: 667.
LDN193189 Hydrochloride是一种选择性转录活性形态发生蛋白（BMP）I型受体抑制剂，BMP受体家族包括激活素受体样激酶（ALK1、ALK2、ALK3和ALK6）[1]。LDN193189 Hydrochloride抑制ALK2和ALK3的IC50值分别为5nM和30nM [2]。LDN193189 Hydrochloride可诱导多能干细胞转化为神经干/祖细胞样细胞[3]。
在体外，LDN193189 Hydrochloride（1、10μM）处理MC3T3-E1细胞12h，可抑制Smad1/5的磷酸化（无论是否与BMP-2共孵育），而不影响单磷酸腺苷激活蛋白激酶（AMPK）磷酸化[4]。LDN193189 Hydrochloride（0-5μM）处理C2C12 细胞，以剂量依赖性方式抑制不同BMP家族成员对 Smad1/5/8、p38和Akt的激活[5]。
在体内，LDN193189 Hydrochloride（0.1-10mg/kg）通过口服治疗炎症性贫血小鼠，抑制了Smad1/5磷酸化，降低了肝脏Id1基因表达和铁调素mRNA水平，效果具有剂量和时间依赖性[6]。LDN193189 Hydrochloride（3mg/kg）通过腹膜内注射治疗乳腺癌骨转移小鼠，表现出促转移特性，加速了溶骨性病变[7]。
| Cell experiment [1]: | |
Cell lines | MC3T3-E1 cells |
Preparation Method | The cells were incubated with BMP-2 (50ng/mL) and/or LDN193189 Hydrochloride (1 and 10μM) for 12 h. Western blot analysis was performed to examine the association between BMP-2-Smad and AMPK signaling. |
Reaction Conditions | 1 and 10µM; 12h |
Applications | Treatments with LDN193189 Hydrochloride suppressed the phosphorylation of Smad1/5 with and without BMP-2 co-incubation, indicating that inhibition of BMP receptor suppressed the effects of endogenous and exogenous BMP-2. In contrast, LDN193189 Hydrochloride did not affect AMPK phosphorylation. |
| Animal experiment [2]: | |
Animal models | C57BL/6 female mice |
Preparation Method | Mice received a dose of LDN193189 Hydrochloride (0.1-10mg/kg), by gavage, at various times (1 to 24hours) prior to sacrifice. After euthanasia, livers were harvested. Proteins were extracted, and levels of total Smad1 and phosphorylated Smad1/5 (p-Smad1/5) were determined by immunoblots. RNA was extracted to measure the levels of mRNAs encoding Id1 and hepcidin by qRT-PCR. |
Dosage form | 0.1-10mg/kg; p.o. |
Applications | LDN193189 Hydrochloride inhibited Smad1/5 phosphorylation at doses above 0.3mg/kg. LDN193189 Hydrochloride at doses above 0.3mg/kg decreased hepatic Id1 gene expression, whereas hepcidin mRNA levels did not decrease. Four hours after oral administration of LDN193189 Hydrochloride, hepatic hepcidin gene expression was decreased at doses ≥ 0.1mg/kg. |
References: [1]Takeno A, Kanazawa I, Notsu M, et al. Inhibition of adenosine monophosphate-activated protein kinase suppresses bone morphogenetic protein-2-induced mineralization of osteoblasts via Smad-independent mechanisms[J]. Endocrine Journal, 2018, 65(3): 291-298. [2]Mayeur C, Kolodziej S A, Wang A, et al. Oral administration of a Bone Morphogenetic Protein (BMP) type I receptor inhibitor prevents the development of anemia of inflammation[J]. 2014. | |
| Cas No. | 1062368-62-0 | SDF | |
| 别名 | LDN 193189 hydrochloride; LDN-193189 hydrochloride | ||
| 化学名 | 4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline tetrahydrochloride | ||
| Canonical SMILES | C1CN(CCN1)C2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC6=CC=CC=C56)N=C3.Cl.Cl.Cl.Cl | ||
| 分子式 | C25H26Cl4N6 | 分子量 | 552.33 |
| 溶解度 | ≥ 16.4 mg/mL in DMSO, ≥ 27.6 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8105 mL | 9.0526 mL | 18.1051 mL |
| 5 mM | 0.3621 mL | 1.8105 mL | 3.621 mL |
| 10 mM | 0.1811 mL | 0.9053 mL | 1.8105 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet