| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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Purity: ≥98%
Smoothened Agonist (SAG) HCl is a potent and cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells. SAG potently activates the Hedgehog signaling pathway in Shh-light 2 cells (EC50 ~ 3 nM). SAG induces pathway activation independently of Ptch proteins. The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumors.
| ln Vitro |
At an EC50 of 3 nM, SAG hydrochloride (0.1 nM-100 μM; 30 h) stimulates firefly luciferase expression in Shh-LIGHT2 cells, which is subsequently inhibited at higher dosages [1]. With an apparent dissociation constant (Kd) of 59 nM for the SAG hydrochloride/Smo complex, SAG hydrochloride (1-1000 nM; 1 h) competes for BODIPY-cyclopamine binding to Smo-expressing Cos-1 cells [1]. Robotnikinin pathway activation mediated by ShhN is inhibited by SAG hydrochloride (100 nM) [2]. SAG hydrochloride (250 nM; 48 h) dramatically boosts SMO protein and mRNA expression in MDAMB231 cells [3]. For 24 hours, both normoxic and hypoxic settings cause CAXII MDAMB231 cells' mRNA expression to rise in response to 250 nM SAG hydrochloride [3]. MDAMB231 cell migration is increased by SAG hydrochloride (250 nM; 24 h) [3].
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| ln Vivo |
In CD-1 mice, SAG hydrochloride (1.0 mM) induced more osteogenesis primarily at the defect border and significantly increased BV/TV at the eight-week time point [4]. SAG hydrochloride (15- 20 mg/kg; ip) universally induces preaxial polydactyly in mice in a dose-dependent manner [5].
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| Animal Protocol |
Animal/Disease Models: Pregnant C57BL/6J mice[5]
Doses: 15, 17, 20 mg/kg Route of Administration: A single ip Experimental Results: Effective in ca. 80% of the embryos and increased Gli1 and Gli2 mRNA expression in the limb bud, with Gli1 mRNA being the most upregulated at the dose of 20 mg/kg. |
| References |
[1]. Chen JK, et al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6.
[2]. Stanton BZ, et al. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009 Mar;5(3):154-6. [3]. Guerrini G, et, al. Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration. J Cell Physiol. 2018 Dec; 233(12): 9799-9811. [4]. Lee S, et al. Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing. Plast Reconstr Surg. 2017 Feb 13. [5]. Fish EW, et al. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. Birth Defects Res A Clin Mol Teratol. 2016 Nov 1. |
| Molecular Formula |
C28H29CL2N3OS
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|---|---|
| Molecular Weight |
526.52
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| CAS # |
2095432-58-7
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| Related CAS # |
SAG;912545-86-9;SAG dihydrochloride;2702366-44-5;(Rac)-SAG;364590-63-6
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| SMILES |
O=C(C1=C(Cl)C2=CC=CC=C2S1)N([C@H]3CC[C@H](NC)CC3)CC4=CC=CC(C5=CC=NC=C5)=C4.[H]Cl
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| InChi Key |
CRWTYWYPPITOOZ-HFSDZXIBSA-N
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| InChi Code |
InChI=1S/C28H28ClN3OS.ClH/c1-30-22-9-11-23(12-10-22)32(28(33)27-26(29)24-7-2-3-8-25(24)34-27)18-19-5-4-6-21(17-19)20-13-15-31-16-14-20/h2-8,13-17,22-23,30H,9-12,18H2,1H31H/t22-,23-
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| Chemical Name |
3-chloro-N-((1r,4r)-4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide hydrochloride
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| Synonyms |
SAG hydrochloride SAG Smo agonist
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~25 mg/mL (~47.48 mM)
DMSO : ~21.67 mg/mL (~41.16 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (4.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (4.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (4.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8993 mL | 9.4963 mL | 18.9926 mL | |
| 5 mM | 0.3799 mL | 1.8993 mL | 3.7985 mL | |
| 10 mM | 0.1899 mL | 0.9496 mL | 1.8993 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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