中文名称:

SAG

中文同义词:

3-氯-N-[反式-4-(甲基氨基)环己基]-N-[[3-(4-吡啶基)苯基]甲基]-苯并[B]噻吩-2-甲酰胺;SMO RECEPTOR激动剂(SAG)

英文名称:

SAG

英文同义词:

3-Chloro-N-[trans-4-(methylamino)cyclohexyl]-N-[[3-(4-pyridinyl)phenyl]methyl]- benzo[b]thiophene-2-carboxamide;SAG;Smoothened Agonist (SAG) free base;CS-1655;3-Chloro-N-[trans-4-(MethylaMino)cyclohexyl]-N-[[3-(4-pyridinyl)phenyl]Methyl]-;SAG (cyclopamine antagonist);SAG (Smo agonist);3-chloro-N-((1r,4r)-4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide

CAS号:

912545-86-9

分子式:

C28H28ClN3OS

分子量:

490.06

EINECS号:

相关类别:

小分子抑制剂，天然产物;小分子抑制剂;细胞生物学试剂;抑制剂;Inhibitors;Intermediates Fine Chemicals;Pharmaceuticals;Heterocyclic Compounds;Heterocycles;Sulfur Selenium Compounds

Mol文件:

912545-86-9.mol

沸点 

688.6±55.0 °C(Predicted)

密度 

1.30±0.1 g/cm3(Predicted)

储存条件 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

形态

lyophilized solid

酸度系数(pKa)

10?+-.0.40(Predicted)

颜色

white to beige

敏感性 

Light Sensitive

稳定性

Light Sensitive

生物活性

SAG 是一种有效的 Smoothened (Smo) 受体激动剂 (EC50=3 nM; Kd=59 nM)。SAG 可激活 Hedgehog 信号通路并抵消 Cyclopamine (HY-17024) 对 Smo 的抑制作用。

靶点

EC50: 3 nM (Smo)

体外研究

SAG (0.1 nM-100 μM; 30 h) induces firefly luciferase expression in Shh-LIGHT2 cells with an EC 50 of 3 nM and then inhibits expression at higher concentrations. SAG (1-1000 nM; 1 h) competes for the binding of BODIPY-cyclopamine to Smo-expressing Cos-1 cells, yielding an apparent dissociation constant (K d ) of 59 nM for the SAG/Smo complex. SAG (100 nM) inhibits the inhibitory effect of ShhN-induced pathway activation by Robotnikinin. SAG (250 nM; 48 h) significantly increases SMO mRNA and protein expression in MDAMB231 cells. SAG (250 nM; 24 and 48 h) increases CAXII mRNA expression in MDAMB231 cells at 24h in normoxic and hypoxic conditions in MDAMB231 cells. SAG (250 nM; 24 h) increases MDAMB231 cells migration.

体内研究

SAG (1.0 mM) induces more osteogenesis mainly at the defect borders and a significant increase in BV/TV at the eight week timepoint in CD-1 mice. SAG (15-20 mg/kg; i.p.) induces pre-axial polydactyly prevalently in a dose-dependent manner in mice. Animal Model: Pregnant C57BL/6J mice Dosage: 15, 17, 20 mg/kg Administration: A single i.p. Result: 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.

Animal Model:

Pregnant C57BL/6J mice

Dosage:

15, 17, 20 mg/kg

Administration:

A single i.p.

Result:

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.

危险品运输编号 

UN 2811 6.1 / PGIII