切换导航

GDC-0449 (Vismodegib)

现货
Catalog No.
A3021
Hedgehog拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
10mg
¥ 500.00
现货
50mg
¥ 650.00
现货
200mg
¥ 1,100.00
现货
500mg
¥ 2,200.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

GDC-0449 (2-chloro-N-[4-chloro-3-pyridin-2-yl-phenyl]-4-methane-sulfonyl benzamide), discovered by high throughput screening of a small molecule compound library followed by subsequent optimization through medical chemistry, is a potent and selective inhibitor of hedgehog (Hh) signaling, a pathway regulating cell growth and differentiation associated in pathogenesis of several cancers. It binds to signaling by smoothened (SMO) and suppresses activation of downstream Hh target genes resulting in the inhibition of Hh signaling pathway. GDC-0449 exhibits anti-tumor activity in a mouse model of medulloblastoma as well as in primary human tumor cell xenograft models of colorectal cancer and pancreatic carcinoma and is currently being evaluated in research projects investigating refractory, locally advanced or metastatic solid tumors.

Reference

Patricia M. LoRusso, Charles M. Rudin, Josina C. Reddy, Raoul Tibes, Glen J. Weiss, Mitesh J. Borad, Christine L. Hann, Julie R. Brahmer, Ilsung Chang, Walter C. Darbonne, Richard A. Graham, Kenn L. Zerivitz, Jennifer A. Low, and Daniel D. Von Hoff. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in Patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011; 17: 2502-2511

文献引用

1. Lima-Fernandes E, Murison A, et al. "Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells." Nat Commun. 2019 Mar 29;10(1):1436. PMID:30926792

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt421.3
Cas No.879085-55-9
FormulaC19H14Cl2N2O3S
SynonymsVismodegib, GDC-0449, HhAntag691, GDC0449, GDC 0449
Solubility≥21.1 mg/mL in DMSO, <2.2 mg/mL in H2O, ≥4.96 mg/mL in EtOH with ultrasonic and warming
Chemical Name2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide
SDFDownload SDF
Canonical SMILESCS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl
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

AsPC-1、MIA PaCa-2、PANC-1和胰腺癌CSC细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,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

10 μM;72小时

应用

该药物处理细胞24小时之内抑制细胞存活,诱导细胞凋亡,在72小时达到最大限度。在所有细胞系中,GDC-0449以剂量依赖的方式诱导细胞凋亡,高达65%。相比在下,在CSCs中,GDC-0449诱导细胞凋亡的效果不是很好。

动物实验[2]:

动物模型

注射MDA PCa 118b细胞的雄性CB17 SCID小鼠

剂量

100 mg/kg,2次/天,21天;口服给药

应用

在GDC-0449治疗组和非治疗组,通过qRT-PCR方法对Shh、Gli1、Gli2、Smo、Ptch1和Sufu进行分析。与对照组相比,治疗组中Gli1和Ptch1的基质表达略微降低。Gli1和Ptch1是活化Hh通路的可靠标记物,这些结果证实了GDC-0449的药效。Gli2和Shh的表达遵循了同样的趋势。与对照组相比,治疗组中Sufu在肿瘤上皮的表达显著降低,免疫组化检测证实了该结果。

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] Singh B N, Fu J, Srivastava R K, et al. Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One, 2011, 6(11): e27306.

[2] Karlou M, Lu J F, Wu G, et al. Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC-0449 in the bone forming prostate cancer xenograft MDA PCa 118b. The Prostate, 2012, 72(15): 1638-1647.

生物活性

描述 Vismodegib (GDC-0449)是一种新型有效的和特异性的Hedgehog抑制剂,IC50值为3 nM,也是P-gp的抑制剂,IC50值为3.0 μM。
靶点 Hedgehog          
IC50 3 nM          

质量控制

化学结构

GDC-0449 (Vismodegib)

相关生物数据

GDC-0449
Gli-luciferase reporter activity of CH310T 1/2 cells transfected with indicated SMO constructs following a dose response of GDC-0449. Values were normalized to maximum activity levels and are mean±SD.

相关生物数据

GDC-0449