LDN-193189 4HCl

体外活性：LDN193189 有效抑制 BMP4 介导的 Smad1、Smad5 和 Smad8 激活，IC50 为 5 nM，并有效抑制 BMP I 型受体 ALK2 和 ALK3 的转录活性，IC50 分别为 5 nM 和 30 nM。此外，LDN193189 还显示出对由组成型活性 ALK2R206H 或 ALK2Q207D 突变蛋白诱导的转录活性的抑制作用。最近的一项研究表明，LDN-193189 可阻断人主动脉内皮细胞动脉粥样硬化过程中氧化 LDL 诱导的活性氧的产生。激酶检测：LDN193189是一种选择性BMP I型受体抑制剂，可有效抑制ALK2和ALK3（IC50分别=5 nM和30 nM），对ALK4、ALK5和ALK7作用较弱（IC50≥500 nM）。细胞测定：将生长的小鼠 PASMC 在六孔板中瞬时转染至 50% 汇合，使用 0.3 μg Id1 启动子荧光素酶报告基因构建体 (BRE-Luc) 结合 0.6 μg 表达组成型活性形式的 BMP I 型受体（caALK2、caALK3）的质粒或 caALK6)。对于两种报告质粒，均使用 0.2 μg pRL-TKRenilla 荧光素酶来控制转染效率。转染后 1 小时开始将 PASMC 与 LDN193189 (2 nM-32 μM) 或载体一起孵育。收获细胞提取物，并使用双荧光素酶测定试剂盒通过萤火虫与海肾荧光素酶活性的比率来量化相对启动子活性。

在出生后第 7 天 (P7) 开启 Ad.Cre 的条件 caALK2 转基因小鼠中，LDN-193189 (3 mg/kg ip) 导致左胫骨和腓骨周围轻度钙化，在 P13 时首次可见，并在 P15 时预防放射学损伤不会导致体重减轻或生长迟缓、自发性骨折、骨密度降低或行为异常。 LDN193189 通过抑制骨形态发生蛋白 (BMP)6 诱导的信号通路使斑马鱼胚胎背侧化，而不影响血管发育。在携带 PCa-118b 肿瘤的小鼠中，LDN-193189 治疗可减弱肿瘤生长并减少肿瘤中的骨形成。在 LDL 受体缺陷 (LDLR-/-) 小鼠中，LDN-193189 可有效抑制动脉粥样硬化的形成。此外，LDN-193189 还表现出对相关血管炎症、成骨活性和钙化的抑制作用。

Nat Med.2008 Dec;14(12):1363-9;Br J Pharmacol.2010 Sep;161(1):140-9.

C₂₅H₂₆CL₄N₆

552.33

1062368-62-0

C1(C2=C3N=CC(C4=CC=C(N5CCNCC5)C=C4)=CN3N=C2)=CC=NC6=CC=CC=C16.Cl.Cl.Cl.Cl

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。