SAG
(Synonyms: Smoothened Agonist) 目录号 : GC12068
SAG(Smoothened Agonist)是一种有效的Smo受体激动剂。
Cas No.:912545-86-9
Sample solution is provided at 25 µL, 10mM.
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SAG (Smoothened Agonist) is an effective Smo receptor agonist. SAG activates the Hedgehog signaling pathway. SAG induces firefly luciferase expression in Shh-LIGHT2 cells with an EC50 of 3nM. In Cos-1 cells expressing Smo, SAG has a Kd of 59nM for the SAG/Smo complex[1-3].
SAG (250nM; 24h) promotes migration of MDA-MB-231 cells[4]. SAG(1μM; 6 days) treatment rescues mitochondrial dysfunction in FXN-deficient astrocytes[5].
SAG(15-20mg/kg；ip) generally induces preaxial polydactylism in a dose-dependent manner in mice[6]. SAG(20μg/g body weight; i.p; 3 times) restores Shh(Sonic hedgehog) signaling, leading to the rescue of BBB function in HIV-infected, humanized mice[7].
References:
[1]. Chen JK, Taipale J, et,al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6. doi: 10.1073/pnas.182542899. Epub 2002 Oct 21. PMID: 12391318; PMCID: PMC137838.
[2]. Bragina O, Sergejeva S, et,al. Smoothened agonist augments proliferation and survival of neural cells. Neurosci Lett. 2010 Sep 27;482(2):81-5. doi: 10.1016/j.neulet.2010.06.068. Epub 2010 Jul 1. PMID: 20600593.
[3]. Stanton BZ, Peng LF, et,al. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009 Mar;5(3):154-6. doi: 10.1038/nchembio.142. Epub 2009 Jan 18. PMID: 19151731; PMCID: PMC2770933.
[4]. Guerrini G, Criscuoli M, et,al. Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration. J Cell Physiol. 2018 Dec;233(12):9799-9811. doi: 10.1002/jcp.26947. Epub 2018 Aug 21. PMID: 30132883.
[5]. Vicente-Acosta A, Giménez-Cassina A, et,al. The smoothened agonist SAG reduces mitochondrial dysfunction and neurotoxicity of frataxin-deficient astrocytes. J Neuroinflammation. 2022 Apr 12;19(1):93. doi: 10.1186/s12974-022-02442-w. PMID: 35413853; PMCID: PMC9006607.
[6]. Fish EW, Parnell SE et,al. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res. 2017 Jan 20;109(1):49-54. doi: 10.1002/bdra.23571. PMID: 27801979; PMCID: PMC5388559.
[7]. Singh VB, Singh MV, et,al. Smoothened Agonist Reduces Human Immunodeficiency Virus Type-1-Induced Blood-Brain Barrier Breakdown in Humanized Mice. Sci Rep. 2016 May 31;6:26876. doi: 10.1038/srep26876. PMID: 27241024; PMCID: PMC4886511.
SAG(Smoothened Agonist)是一种有效的Smo受体激动剂。SAG能够激活 Hedgehog 信号通路。SAG在Shh-LIGHT2细胞中可促使萤火虫荧光素酶的表达，EC50为3nM。在表达Smo的Cos-1细胞中，SAG与SAG/Smo复合物的Kd为59nM[1-3]。
SAG(250nM;24h)促进MDA-MB-231细胞的迁移[4]。SAG(1μM; 6 days)治疗可挽救FXN缺陷的星形胶质细胞线粒体功能障碍[5]。
SAG(15-20mg/kg；ip) 在小鼠中以剂量依赖性方式普遍诱导轴前多指畸形[6]。在HIV感染的人源化小鼠中，SAG(20μg/g body weight; i.p; 3 times)恢复Shh(Sonic hedgehog)信号，导致血脑屏障功能的恢复[7]。
| Cell experiment [1]: | |
Cell lines | MDAMB 231 cells |
Preparation Method | Cells were seeded at a concentration of 2 × 105 cells in 12 well/plates. When treated with compounds, cells were pretreated for 24h with SAG 250nM or DMSO as a control. The day after, a scratch was done using a p200 tip to the confluent monolayer; cells were then washed with PBS and resuspended in 1ml RPMI supplemented with 10% FBS and AraC (Cytosine β-D-arabinofuranoside; a selective inhibitor of DNA synthesis; 2.5µg/ml). |
Reaction Conditions | 250nM;24h |
Applications | SAG promotes migration of MDA-MB-231 cells. |
| Animal experiment [2]: | |
Animal models | HIV-infected, humanized mice |
Preparation Method | Mice were injected on alternate days with SAG (20μg/g body weight) or vehicle control, DMSO, for a total of 3 injections. Evans blue exclusion assay was performed to measure BBB permeability. |
Dosage form | 20μg/g body weight; i.p; 3 times |
Applications | SAG rescues BBB(Blood Brain Barrier) integrity. |
References: | |
| Cas No. | 912545-86-9 | SDF | |
| 别名 | Smoothened Agonist | ||
| 化学名 | 3-chloro-N-((1r,4r)-4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide | ||
| Canonical SMILES | CN[C@@]1([H])CC[C@@](N(C(C2=C(Cl)C3=CC=CC=C3S2)=O)CC4=CC(C5=CC=NC=C5)=CC=C4)([H])CC1 | ||
| 分子式 | C28H28ClN3OS | 分子量 | 490.06 |
| 溶解度 | ≥ 24.5mg/mL in DMSO, ≥ 16.3mg/mL in Water with ultrasonic and warming | 储存条件 | 4°C, protect from light |
| 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 | 2.0406 mL | 10.2028 mL | 20.4057 mL |
| 5 mM | 0.4081 mL | 2.0406 mL | 4.0811 mL |
| 10 mM | 0.2041 mL | 1.0203 mL | 2.0406 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet