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GDC-0994

现货
Catalog No.
B5817
ERK1/2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,400.00
Ship with 5-10 days
5mg
¥ 1,000.00
Ship with 10-15 days
10mg
¥ 1,500.00
Ship with 10-15 days
50mg
¥ 5,000.00
Ship with 10-15 days

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Background

GDC-0994 is a potent and selective inhibitor of ERK1/2 with IC50 values of 1.1 and 0.3 nM, respectively [1].

The extracellular-signal-regulated kinases (ERK1 and ERK2) are members of the MAP kinase family and act downstream of the RAS/RAF/MEK/ERK signaling cascade that are commonly activated by upstream oncogenic signaling or oncogenic mutations in BRAF or RAS. ERK1/2 play important roles in proliferation, differentiation and cell cycle progression [1].

GDC-0994 is an orally available and potent ERK1/2 inhibitor with potential antineoplastic activity. In mice bearing KRAS-mutant and BRAF-mutant human xenograft tumors, GDC-0994 exhibited significant single-agent activity and inhibited phospho-p90RSK [1]. When orally administration, GDC-0994 inhibited both activation of ERK-mediated signal transduction pathways and ERK phosphorylation, which then inhibited ERK-dependent tumor cell survival and proliferation.

References:
[1].  Robarge K, Schwarz J, Blake J, et al. Abstract DDT02-03: Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development. AACR Annual Meeting, 2014, San Diego, CA.

文献引用

1. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758
2. Zhang XH, Li CY, et al. "Pro-angiogenic activity of isoliquiritin on HUVECs in vitro and zebrafish in vivo through Raf/MEK signaling pathway." Life Sci. 2019 Apr 15;223:128-136. PMID:30876941
3. Duan T, Cil O, et al. "Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea." JCI Insight. 2019 Feb 21;4(4). pii: 126444. PMID:30668547

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt440.86
Cas No.1453848-26-4
FormulaC21H18ClFN6O2
Solubility≥44.1mg/mL in DMSO
Chemical Name(S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one
SDFDownload SDF
Canonical SMILESCN1C(NC2=NC=CC(C(C=CN3[C@](C4=CC(F)=C(Cl)C=C4)([H])CO)=CC3=O)=N2)=CC=N1
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

BRAFV600E细胞系

溶解方法

该化合物在DMSO中的溶解度大于22.1 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

应用

在BRAFV600E细胞系中,与BRAF抑制剂相比,GDC-0994抑制信号通路和细胞增殖。

动物实验 [2]:

动物模型

携带KRAS突变体和BRAF突变体的人异种移植肿瘤的小鼠,HT29结肠直肠癌异种移植模型。

给药剂量

口服,每天

应用

在小鼠KRAS突变体和BRAF突变体人异种移植肿瘤中,每日口服GDC-0994造成明显的单一药剂活性。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Nambu T, Iwai K, Shibata S, et al. Identification of driver of anti-tumor activity of TAK-931 in human colorectal cancer xenograft model[J]. European Journal of Cancer, 2016, 69: S30.

[2]. Robarge K, Schwarz J, Blake J, et al. Abstract DDT02-03: Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development. AACR Annual Meeting, 2014, San Diego, CA.

质量控制

化学结构

GDC-0994

相关生物数据

GDC-0994

相关生物数据

GDC-0994