SAG - Smo Agonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESAGCat. No.: HY-12848CAS No.: 912545-86-9分式: CHClNOS分量: 490.06作靶點: Smo作通路: Stem Cell/Wnt儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect fromlight)溶解性數(shù)據(jù)體外實驗 DMSO : 38 mg/mL (77.54 mM)* means solub

2、le, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0406 mL 10.2028 mL 20.4057 mL5 mM 0.4081 mL 2.0406 mL 4.0811 mL10 mM 0.2041 mL 1.0203 mL 2.0406 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)

3、天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 10 mg/mL (20.41 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 10 mg/mL (20.41 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 10 m

4、g/mL (20.41 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 SAG種有效的 Smo 受體 激動劑，能夠活化 Hedgehog 信號通路，Kd 值為 59 nM。IC50 & Target Kd: 59 nM (Smo) 1體外研究 SAG acts downstream of Ptch1 in the Hh pathway and counteracts cyclopamine inhibition of Smo. SAGinduces firefl

5、y luciferase expression in Shh-LIGHT2 cells with an EC50 of 3 nM and then inhibits expressionat higher concentrations. In Smo-expressing Cos-1 cells, SAG yields an apparent dissociation constant (KD)of 59 nM for the SAG/Smo complex 1. SAG and purmorphamine verride the inhibitory effect of robotnikin

6、insince Smo functions downstream of Shh/Ptc1 2.體內(nèi)研究 In CD-1 mice, SAG (1.0 mM) or NELL-1 (600 g/ml) alone results in increased bone formation at 4 and 8weeks, but significantly greater bone formation with both components combined (SAG + NELL-1). Thecombination of the two compounds exhibits a signifi

7、cant increase in new bone formation, accompanied byincreased defect vascularization 3. SAG (15, 17, or 20 mg/kg, i.p.) induces pre-axial polydactyly prevalently.The highest SAG dose is effective in ca. 80% of the embryos and increased Gli1 and Gli2 mRNA expressionin the limb bud, with Gli1 mRNA bein

8、g the most upregulated 4.PROTOCOLAnimal GD 9:6 hr females are weighed, given a single intraperitoneal SAG injection (6, 6, and 7 for the 15, 17, andAdministration 4 20 mg/kg doses, respectively) or vehicle (lactated Ringers solution; 9 litters), and returned to their homecage. GD 9:6 is a sensitive

9、period for inducing forelimb malformations by retinoic acid and ethanoladministration. For SAG dose-response studies, GD 15 embryos are collected, examined for the number andappearance of the digits on each limb. For whole-mount in situ hybridization studies, embryos are collectedat GD 9:10 hr in ic

10、e-cold RNase-free phosphate-buffered saline (PBS), fixed in 4% paraformaldehyde, rinsedwith PBS, dehydrated in methanol and stored at -20C.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Development. 2018 Sep 20;145(18). pii: dev164830. Mole

11、cules. 2017 Dec 31;23(1). pii: E85. J Pharm Biomed Anal. 2017 Aug 5;142:201-209. Drug Dev Res. 2019 Aug 12.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. 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. S

12、tanton BZ, et al. A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009 Mar;5(3):154-6.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. Lee S, et al. Combining Smoothened Agonist (SAG) and NEL-like protein-1 (NELL-1) Enhances Bone Healing. Plast Reconstr Surg.2017 Feb 134. Fish EW, et al. Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice. BirthDefects Res A Clin Mol Teratol. 2016 Nov 1McePdfHeight