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LY3009120

现货
Catalog No.
A8716
Pan-RAF和RAF二聚体抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,030.00
现货
25mg
¥ 3,350.00
现货
100mg
¥ 6,990.00
Ship with 10-15 days

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Background

LY3009120 is a pan-RAF and RAF dimer inhibitor. It inhibits BRAF WT, CRAF, WT, BRAFV600E, and BRAFV600E+G468A with the IC50 values of 9.1, 15, 5.8, and 17 nM, respectively. [1]

RAF is family of serine/threonine-protein kinase mediates Ras GTPases and the MAPK/ERK cascade. It involves in proliferation, differentiation, apoptosis, survival and oncogenic transformation. [1]

In NRAS mutant SK-Mel2 cells or KRAS mutant HCT116 cells, LY3009120 inhibits the kinase activity of CRAF in a dose-dependent manner and induces BRAF/CRAF heterodimerization. It also blocks Phospho-MEK and -ERK and induces minimal paradoxical activation in RAS mutant Cells. Moreover, treatment of BRAF V600E A375 melanoma cells by LY3009120 for 24 hr predominantly induces a G0/G1 arrest with more than 95% cells in G0/G1 phase. [1]

In nude rats bearing A375 xenograft tumors, oral LY3001920 treatment exerts a dose-dependent inhibition of phospho-MEK and –ERK. 15 or 30 mg/kg LY3009120 shows near complete tumor regression in nude rats bearing PDX tumors. [1]

Reference:
1.  Peng SB, Henry JR, Kaufman MD et al. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers. Cancer Cell. 2015 Sep 14;28(3):384-98.

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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt424.51
Cas No.1454682-72-4
FormulaC23H29FN6O
Solubility≥4.25mg/mL in DMSO with ultrasonic and warming
Chemical Name1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)pyrido[2,3-d]pyrimidin-3-yl)phenyl)urea
SDFDownload SDF
Canonical SMILESCC1=NC2=NC(NC)=NC=C2C=C1C3=CC(NC(NCCC(C)(C)C)=O)=C(F)C=C3C
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

A375细胞和HCT116细胞

溶解方法

该化合物可溶于DMSO。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

0.5 μM,24,72 h

应用

LY3009120可抑制BRAF或NRAS突变的黑素瘤细胞增殖。它还诱导RAS或BRAF突变的肿瘤细胞细胞周期G0/G1阻滞和细胞凋亡。

动物实验[2]:

动物模型

带有异种移植肿瘤的雌性NIH裸鼠

剂量

口服给药,5,10或15mg/kg,每天两次

应用

5,10或15mg/kg LY3009120给药带有黑色素瘤BRAF V600E A375异种移植肿瘤的大鼠,每天两次,以剂量依赖的方式诱导肿瘤生长抑制和消退。

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]. Peng S B, Henry J R, Kaufman M D, et al. Inhibition of RAF isoforms and active dimers by LY3009120 leads to anti-tumor activities in RAS or BRAF mutant cancers[J]. Cancer Cell, 2015, 28(3): 384-398.

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