SAG (Synonyms: Smoothened Agonist) |
رقم الكتالوجGC12068 |
SAG هو ناهض قوي لمستقبلات (Smo) (EC50 = 3 نانومتر ؛ Kd = 59 نانومتر)ينشط SAG مسار إشارات القنفذ ويقاوم تثبيط السيكلوبامين لـ Smo
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Cas No.: 912545-86-9
Sample solution is provided at 25 µL, 10mM.
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.
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 | |
المرادفات | Smoothened Agonist | ||
Chemical Name | 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 | ||
Formula | C28H28ClN3OS | M.Wt | 490.06 |
الذوبان | ≥ 24.5mg/mL in DMSO, ≥ 16.3mg/mL in Water with ultrasonic and warming | Storage | 4°C, protect from light |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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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 |
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- Purity: >99.50%
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Average Rating: 5
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