GDC-0994
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-0994是ERK1/2的有效选择性抑制剂,IC50值分别为1.1和0.3 nM[1].
胞外信号调节激酶ERK1和ERK2属于MAP激酶家族,是RAS/RAF/MEK/ERK信号级联的下游,通常由上游致癌信号或BRAF与RAS的致癌突变激活.ERK1/2在细胞增殖\分化和细胞周期进程中发挥重要作用[1].
GDC-0994是一种口服有效的ERK1/2抑制剂,具有潜在的抗肿瘤活性.在KRAS突变和BRAF突变人类肿瘤异种移植小鼠中,GDC-0994具有显著的单药活性,抑制磷酸化p90RSK[1].口服给药GDC-0994抑制ERK介导的信号转导途径活化和ERK磷酸化,随后抑制ERK依赖性肿瘤细胞存活和增殖.
参考文献:
[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.
- 1. Jr-Ming Yang, Wei-Yu Chi, et al. "Deciphering cell signaling networks with massively multiplexed biosensor barcoding." Cell. 2021 Dec 9;184(25):6193-6206.e14. PMID: 34838160
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- 3. 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
- 4. Hin Chu, Yuxin Hou, et al. "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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 440.86 |
Cas No. | 1453848-26-4 |
Formula | C21H18ClFN6O2 |
Solubility | ≥44.1 mg/mL in DMSO; insoluble in H2O; ≥19.2 mg/mL in EtOH |
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 |
SDF | Download SDF |
Canonical SMILES | CN1C(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 | 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 |
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. |
质量控制和MSDS
- 批次: