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RAF265

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Chemical Structure| 927880-90-8 同义名 : CHIR-265
CAS号 : 927880-90-8
货号 : A342718
分子式 : C24H16F6N6O
纯度 : 99%+
分子量 : 518.414
MDL号 : MFCD16659061
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(48.22 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 8 mg/mL(15.43 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 3 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • VEGFR2

    VEGFR2, EC50:30 nM

  • B-Raf

    B-Raf, IC50:3 nM-60 nM
描述 B-Raf protein is a key mediator in the MAPK signaling pathway that involved in the pathogenesis of multiple cancers. An important V600E mutation has been shown to cause constitutive B-Raf activation. RAF265 is an oral molecule inhibitor of both mutant BRAFV600E and VEGFR2 with EC50 values of 0.14 μM and 0.19 μM, respectively[5]. The IC50 values of RAF265 against of BRAFV600E, wild-type BRAF, VEGFR, and C-RAF were 0.5, 70, 20 and 19μM, respectively[6]. In HT29 and MDAMB231 cells, RAF265 inhibited cell viability with IC20 values of 1-3μM and IC50 values of 5-10μM. In A549 and HCT116 cells, the IC2020 values of RAF265 were 1μM for both cell lines, but the IC50 values were more than 10μM. Additionally, treatment with RAF265 at the concentrations of 1-10μM decreased MEK phosphorylation in BRAF-mutated cell lines. In HCT116, HT29, and MDAMB231 cell lines, increasing doses of RAF265 also decreased the phosphorylation of S6 ribosomal protein. In mice inoculated with HCT116 cancer cells, the time to achieve a relative 10 times of the initial tumor volume was 25 days in the RAF265 group (12 mg/kg, once per day), compared to 20 days in the control group. The combination of RAF265 and RAD001 at a dose of 12 mg/kg/d delayed the tumor growth for 5 days [7].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A375 cells Proliferation assay Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant, IC50=0.04 μM 26396681
human Malme-3M cells Function assay Inhibition of B-RAF V600E mutant in human Malme-3M cells assessed as phosphorylation of ERK, IC50=0.04 μM 26396681
SK-MEL-28 cells Function assay Inhibition of B-RAF V600E mutant in human SK-MEL-28 cells assessed as phosphorylation of ERK, IC50=0.14 μM 26396681
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.64mL

1.93mL

0.96mL

19.29mL

3.86mL

1.93mL
参考文献

[1]Mordant P, Loriot Y, et al. Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination. Mol Cancer Ther. 2010 Feb;9(2):358-68.

[2]Zitzmann K, de Toni E, et al. The novel Raf inhibitor Raf265 decreases Bcl-2 levels and confers TRAIL-sensitivity to neuroendocrine tumour cells. Endocr Relat Cancer. 2011 Mar 21;18(2):277-85.

[3]Williams TE, Subramanian S, et al. Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma. ACS Med Chem Lett. 2015 Aug 3;6(9):961-5.

[4]Chow AK, Cheng NS, et al. Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26(+) cancer stem cells in colorectal carcinoma. Mol Cancer. 2015 Apr 11;14:80.

[5]Huang T, Karsy M, Zhuge J, Zhong M, Liu D. B-Raf and the inhibitors: from bench to bedside. J Hematol Oncol. 2013 Apr 25;6:30. doi: 10.1186/1756-8722-6-30. PMID: 23617957; PMCID: PMC3646677.

[6]Williams TE, Subramanian S, Verhagen J, McBride CM, Costales A, Sung L, Antonios-McCrea W, McKenna M, Louie AK, Ramurthy S, Levine B, Shafer CM, Machajewski T, Renhowe PA, Appleton BA, Amiri P, Chou J, Stuart D, Aardalen K, Poon D. Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma. ACS Med Chem Lett. 2015 Aug 3;6(9):961-5. doi: 10.1021/ml500526p. PMID: 26396681; PMCID: PMC4569875.

[7]Mordant P, Loriot Y, Leteur C, Calderaro J, Bourhis J, Wislez M, Soria JC, Deutsch E. Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination. Mol Cancer Ther. 2010 Feb;9(2):358-68. doi: 10.1158/1535-7163.MCT-09-1014. Epub 2010 Feb 2. PMID: 20124452.