切换导航

SAG

现货
Catalog No.
B5837
Hh和Smo激动剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,700.00
现货
2mg
¥ 850.00
现货
5mg
¥ 1,750.00
现货
25mg
¥ 5,250.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

SAG is a synthetic chlorobenzothiophene-containing Hh pathway agonist that regulates smo activity. It is a SMO agonist at EC50 of 3 nM and but inhibits hedgehog signaling at >1 μM. [1]

Smoothened (SMO) is a GPCR-like receptor that mediates hedgehog signaling with Patched to regulate gene expression through the Gli transcription factors. It is plays an important role for embryogenesis and adults tissue homeostasis

In a mouse cultured cell assay (Shh-LIGHT2), SAG induces pathway activation (EC50 ≈3 nM). It differs in that pathway activity decreases dramatically as SAG concentration surpasses 1 μM. [1] SAG binds directly to the SMO heptahelical bundle. SAG dose dependently blocks this association and produces apparent dissociation constant (KD) of 59 nM for the SAG/SMO complex. [2]

SAG also antagonizes GC’s antiproliferative effects in CGNP P4 wild-type mice primary cultures. At 15-240 nM, SAG prevents the neurotoxic effects of glucocorticoids without interfering with the beneficial effects of glucocorticoids on lung maturation. [2]

References:
1.  Chen JK, Taipale J, Young KE et al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6.
2.  Heine VM, Griveau A, Chapin C et al. A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury. Sci Transl Med. 2011 Oct 19;3(105):105ra104.

Chemical Properties

StorageStore at -20°C
M.Wt490.06
Cas No.912545-86-9
FormulaC28H28ClN3OS
Solubility≥24.5mg/mL in DMSO, ≥16.3mg/mL in H2O with ultrasonic and warming
Chemical Name3-chloro-N-((1r,4r)-4-(methylamino)cyclohexyl)-N-(3-(pyridin-4-yl)benzyl)benzo[b]thiophene-2-carboxamide
SDFDownload SDF
Canonical SMILESCN[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
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

Shh-LIGHT细胞系

溶解方法

在DMSO中的溶解度> 24.5mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0.1~100 μM

应用

SAG诱导小鼠培养细胞中的Hh通路活化,EC50为3nM。但是,当SAG浓度超过1μM时,通路活性显著降低。

动物实验[2]:

动物模型

P4野生型小鼠

剂量

SAG(20μg/g),泼尼松龙(0.67μg/g),7日,每日一次

应用

SAG在治疗剂量下可有效预防糖皮质激素引起的小鼠新生儿小脑发育异常。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Chen JK, Taipale J, Young KE et al. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071-6.

[2] Heine VM, Griveau A, Chapin C et al. A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury. Sci Transl Med. 2011 Oct 19;3(105):105ra104.

质量控制

化学结构

SAG