GDC-0449 (Vismodegib)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
GDC-0449 [2-chloro-N-[4-chloro-3-pyridin-2-yl-phenyl]-4-methane-sulfonyl benzamide]是通过小分子化合物文库的高通量筛选,并经过医用化学的后续优化而获得的,是一种有效的和选择性的Hedgehog (Hh)信号抑制剂。Hh信号通路调控与多种癌症的发病相关的细胞生长和分化。GDC-0449通过与Smoothened (SMO)结合,抑制下游Hh靶基因的激活,从而抑制Hh信号通路。在髓母细胞瘤小鼠模型和原发性人大肠癌和胰腺癌细胞异种移植模型中,GDC-0449具有抗肿瘤活性,目前正用于局部晚期或转移性实体瘤的研究。
参考文献:
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
- 1. Yakinthi Chrisochoidou, Rajat Roy, et al. "Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells." Cell Death Dis. 2023 Nov 8;14(11):725. PMID: 37938546
- 2. Yuan Han Teh, Rui Jing, et al. "More than just a KRAS inhibitor: DCAI abrogates the self-renewal of pancreatic cancer stem cells in vitro."Oncologie. September 27, 2023.
- 3. Qing Gao, Xuhong Chang, et al. "LncRNA MEG3 restrained pulmonary fibrosis induced by NiO NPs via regulating hedgehog signaling pathway‐mediated autophagy." Environ Toxicol. 2022 Jan;37(1):79-91. PMID: 34608745
- 4. Su-Fen Wei, Dan-Hua He, et al. "Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma." Biochem Pharmacol. 2021 Aug;190:114593. PMID:33964282
- 5. Kowolik CM, Lin M, et al. "Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer." J Exp Clin Cancer Res. 2019 Oct 28;38(1):431. PMID:31661013
- 6. 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
Physical Appearance | A solid |
Storage | Desiccate at -20°C |
M.Wt | 421.3 |
Cas No. | 879085-55-9 |
Formula | C19H14Cl2N2O3S |
Synonyms | Vismodegib, GDC-0449, HhAntag691, GDC0449, GDC 0449 |
Solubility | ≥21.08 mg/mL in DMSO; insoluble in H2O; ≥4.96 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide |
SDF | Download SDF |
Canonical SMILES | CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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 |
质量控制和MSDS
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