SIS3 HCl
(Synonyms: SIS3 盐酸盐) 目录号 : GC17191
SIS3 HCl是一种Smad3抑制剂，可抑制Smad3 的磷酸化， IC50 为3 μM。
Cas No.:521984-48-5
Sample solution is provided at 25 µL, 10mM.
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SIS3 HCl is a Smad3 inhibitor that inhibits the phosphorylation of Smad3 with an IC50 of 3 μM [1].
SIS3 HCl can dose-dependently eliminate enhanced p3TP-lux luciferase activity, attenuated Smad3 phosphorylation induced by transforming growth factor (TGF-1) and the interaction between Smad3 and Smad4, but SIS3 HCl does not affect Smad2 phosphorylation. SIS3 HCl attenuates the effects of TGF-1 by reducing transcriptional activity and inhibits differentiation of adult myofibroblasts via TGF-1[1]. SIS3 HCl (10 μM) in ML-12 cells blocked TGF-β-mediated Smad3 phosphorylation, while total Smad2/3 levels remained unchanged[2].
In a study of Tie2-Cre; Loxp-EGFP mice, SIS3 HCl (2.5 mg/kg/day) inhibited Smad3 activation in streptozotocin (STZ)-induced diabetic nephropathy. SIS3 HCl eliminates endothelial mesenchymal transition, reduces renal fibrosis, and slows the progression of kidney disease[3]. SIS3 HCl (5 mg/kg) significantly reduced body weight, adiposity, and fasting blood glucose in high-fat diet-induced type 2 diabetes mellitus (T2DM) model mice, and also improved insulin sensitivity and oral glucose tolerance in mice[4].
References:
[1] Jinnin M et al. Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol. 2006 Feb;69(2):597-607.
[2] Leiting S, Seidl S, Martinez-Palacian A, Muhl L, Kanse SM. Transforming Growth Factor-β (TGF-β) Inhibits the Expression of Factor VII-activating Protease (FSAP) in Hepatocytes. J Biol Chem. 2016 Sep 30;291(40):21020-21028.
[3] Li J et al. Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes.2010 Oct;59(10):2612-24.
[4] Wang D C, Yan T T, Chen B, et al. SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice[J]. Fundamental & Clinical Pharmacology, 2021, 35(2): 389-396.
SIS3 HCl是一种Smad3抑制剂，可抑制Smad3 的磷酸化， IC50 为3 μM[1]。
SIS3 HCl可剂量依赖性地消除增强的p3TP-lux荧光素酶活性，减弱转化生长因子（TGF-1）诱导的Smad3磷酸化以及Smad3与Smad4的相互作用，但SIS3 HCl并不影响Smad2的磷酸化。SIS3 HCl通过减少转录活性来减轻TGF-1的作用，并通过TGF-1抑制成肌成纤维细胞的分化[1]。ML-12细胞中SIS3 HCl（10 μM）阻断了TGF-β介导的Smad3磷酸化，而总Smad2/3水平保持不变[2]。
在对Tie2-Cre；Loxp-EGFP小鼠的研究中，SIS3 HCl（2.5 mg/kg/day）可以抑制链脲佐菌素（STZ）诱导的糖尿病性肾病中Smad3的激活。SIS3 HCl可以消除内皮间质转化，减少肾脏纤维化，减缓肾病的进展[3]。SIS3 HCl（5mg/kg）能显著降低高脂饮食诱导的2型糖尿病（T2DM）模型小鼠的体重、脂肪量、空腹血糖，还能改善小鼠的胰岛素敏感性和口服葡萄糖耐量[4]。
| Cell experiment [1]: | |
Cell lines | HK-2 cells |
Preparation Method | Cells were incubated with 0.1% DMSO, or 5 μM SIS3 HCl for 1 h and then incubated with or without 25 μm CdCl2 (Cd) for 30 h. The viability of cells was determined by trypan blue exclusion assay. |
Reaction Conditions | 5 μM, 1 h |
Applications | SIS3 HCl inhibited cadmium-induced HK-2 cell death. |
| Animal experiment [2]: | |
Animal models | T2DM mouse model |
Preparation Method | The diagnosed type 2 diabetic mice were randomly divided into three groups, including T2DM + saline group, T2DM + vehicle group, and T2DM + SIS3 HCl treatment group. Fasting blood glucose, oral glucose tolerance, and insulin tolerance data were measured after 45 d of continuous drug administration. |
Dosage form | 5 mg/kg, 45 days, i.p. |
Applications | SIS3 HCl significantly reduced body weight, adiposity, fasting blood glucose and also improved insulin sensitivity and oral glucose tolerance in mice. |
References: [1] Fujiki K, Inamura H, Sugaya T, Matsuoka M. Blockade of ALK4/5 signaling suppresses cadmium- and erastin-induced cell death in renal proximal tubular epithelial cells via distinct signaling mechanisms. Cell Death Differ. 2019 Nov;26(11):2371-2385. [2] Wang D C, Yan T T, Chen B, et al. SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice[J]. Fundamental & Clinical Pharmacology, 2021, 35(2): 389-396. | |
| Cas No. | 521984-48-5 | SDF | |
| 别名 | SIS3 盐酸盐 | ||
| 化学名 | (E)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one hydrochloride | ||
| Canonical SMILES | CN1C(C2=CC=CC=C2)=C(C3=C1N=CC=C3)/C([H])=C([H])/C(N4CCC5=CC(OC)=C(OC)C=C5C4)=O.Cl | ||
| 分子式 | C28H28ClN3O3 | 分子量 | 489.99 |
| 溶解度 | ≥ 49 mg/mL in DMSO, ≥ 11 mg/mL in EtOH with ultrasonic and warming | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0409 mL | 10.2043 mL | 20.4086 mL |
| 5 mM | 0.4082 mL | 2.0409 mL | 4.0817 mL |
| 10 mM | 0.2041 mL | 1.0204 mL | 2.0409 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
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet