RAF265 (CHIR-265)

目录号：S2161 Purity: 99.97%

RAF265 (CHIR-265)是一种有效的选择性C-Raf/B-Raf/B-Raf V600E抑制剂，IC50为3-60 nM，对VEGFR2磷酸化表现出有效的抑制作用，无细胞试验中EC50为30 nM。RAF265 (CHIR-265)可诱导细胞周期阻滞和凋亡。Phase 2。

RAF265 (CHIR-265) Chemical Structure

CAS: 927880-90-8

规格	价格	库存
10mM (1mL in DMSO)	1956.12	现货
5mg	1415.74	现货
10mg	2629.71	现货
25mg	4561.83	现货
100mg	13677.3	现货
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产品质控

批次：纯度： 99.97%

99.97

RAF265 (CHIR-265)相关产品

相关靶点	C-Raf/Raf-1 B-Raf A-raf	点击展开
相关产品	PLX-4720 LY3009120 AZ 628 GDC-0879 SB590885 TAK-632 GW5074 Avutometinib PLX7904 Plixorafenib (PLX8394) ZM 336372 Naporafenib (LXH254) Lifirafenib (BGB-283) Agerafenib (CEP-32496) Tovorafenib (MLN2480) Belvarafenib B-Raf inhibitor 1 (Compound 13) dihydrochloride RAF709 CCT196969	点击展开
相关化合物库	激酶抑制剂库 MAPK抑制剂库细胞周期化合物库 TGF-beta/Smad信号通路库抗阿尔茨海默病化合物库	点击展开

细胞实验数据示例

细胞系	实验类型	给药浓度	孵育时间	活性描述	文献信息
A375M	Function assay	100 mg/kg	48 hrs	Inhibition of B-RAF V600E mutant in mouse xenografted with human A375M cells assessed as reduction of phospho-MEK level in tumor at 100 mg/kg, po q24 after 48 hrs by Western blot analysis	26396681
A375M	Function assay	100 mg/kg	48 hrs	Inhibition of B-RAF V600E mutant in mouse xenografted with human A375M cells assessed as reduction of phospho-MEK level in tumor at 100 mg/kg, po q2d after 48 hrs by Western blot analysis	26396681
A375M	Function assay	30 to 100 mg/kg	4 hrs	Inhibition of B-RAF V600E mutant in mouse xenografted with human A375M cells assessed as reduction of phospho-MEK level in tumor at 30 to 100 mg/kg, po q2d measured after 4 hrs post-third dose by Western blot analysis	26396681
A375M	Antitumor assay	10 to 100 mg/kg	30 days	Antitumor activity against human A375M cells xenografted in mouse assessed as tumor regression at 10 to 100 mg/kg, po q2d measured up to 30 days	26396681
A375M	Function assay	100 mg/kg		fCmin in mouse xenografted with human A375M cells at 100 mg/kg, po q2d, fCmin=0.5μM.	26396681
VERO-E6	Function assay		48 hrs	Toxicity CC50 against VERO-E6 cells determined at 48 hours by high content imaging (same conditions as 2_LEY without exposure to 0.01 MOI SARS CoV-2 virus), CC50=9.19μM.	ChEMBL
VERO-E6	Function assay		48 hrs	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of VERO-E6 cells after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging, IC50=14.64μM.	ChEMBL
A375	Function assay			Inhibition of B-RAF V600E mutant in human A375 cells assessed as phosphorylation of ERK, IC50=0.04μM.	26396681
A375M	Growth inhibition assay			Growth inhibition of A375M cells, IC50=0.14μM.	21576023
MALME-3M	Growth inhibition assay			Growth inhibition of MALME-3M cells, IC50=0.14μM.	21576023
SK-MEL-28	Growth inhibition assay			Growth inhibition of SK-MEL-28 cells, IC50=0.14μM.	21576023
Malme-3M	Function assay			Inhibition of B-RAF V600E mutant in human Malme-3M cells assessed as phosphorylation of ERK, IC50=0.04μM.	26396681
WM-1799	Function assay			Inhibition of B-RAF V600E mutant in human WM-1799 cells assessed as phosphorylation of ERK, IC50=0.04μM.	26396681
MALME-3M	Antiproliferative assay			Antiproliferative activity against human MALME-3M cells harboring B-RAF V600E mutant, IC50=0.04μM.	26396681
A375	Antiproliferative assay			Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant, IC50=0.04μM.	26396681
WM1799	Antiproliferative assay			Antiproliferative activity against human WM1799 cells harboring B-RAF V600E mutant, IC50=0.04μM.	26396681
SK-MEL-28	Function assay			Inhibition of B-RAF V600E mutant in human SK-MEL-28 cells assessed as phosphorylation of ERK, IC50=0.14μM.	26396681
SK-MEL-28	Antiproliferative assay			Antiproliferative activity against human SK-MEL-28 cells harboring B-RAF V600E mutant, IC50=0.16μM.	26396681
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
点击查看更多细胞系数据

生物活性

产品描述

特性

CHIR-265是有效的c-Raf/B-Raf/mutB-Raf选择性抑制剂，有效抑制含Ras/Raf 通路突变的肿瘤细胞增殖和存活,作用于一大批临床前期模型具有高效性。

靶点

VEGFR2 ^[1] (Cell-free assay)	B-Raf ^[1] (Cell-free assay)
30 nM(EC50)	3 nM-60 nM

体外研究(In Vitro)
体外研究活性	RAF265 是有效的新型BRAF/VEGFR-2抑制剂, 作用于A375M(^V600EBRAF)人黑色素瘤细胞系，降低肿瘤糖代谢和FDG累积。RAF265抑制2-脱氧-2-[¹⁸F]氟代-D-葡萄糖(FDG)累积，这种作用存在剂量依赖性。 RAF265 显著调节糖代谢, 嘧啶代谢,和凋亡通路。RAF265抑制VEGF诱导的血管生成和突变BRAF, 血管生成通路和新的用于血管生成成像的新兴示踪剂将被用于评估双重作用机制的相对优势。^[1]RAF265作用于HT29和 MDAMB231 细胞中的BRAF，具有显著活性，IC20为1到3 μM，IC50为5 到10 μM。使用浓度为1到10 μM RAF265 处理BRAF突变的细胞系，降低MEK磷酸化。 1 μM RAF265处理非 BRAF突变的细胞系，却提高MEK磷酸化, RAF265浓度达到 5 μM时可逆转这种变化。加入RAD001，增强RAF265作用于 HCT116细胞系的毒性。^[2] RAF265处理，降低 pERK水平，这种作用存在剂量依赖性，0.5 mM RAF265 处理2小时后，完全阻断 G2-M期进展, 导致G2-M期细胞为0%。^[3] RAF265抑制表达^V600EBRAF的细胞生长，比作用于^WTBRAF细胞选择性高14倍，比作用于对选择性 BRAF抑制剂不敏感的守卫-突变^T529N, ^V600EBRAF细胞高7倍, 说明RAF265的细胞内靶点是BRAF。^[4]
激酶实验	激酶组siRNA合成致死扫描和数据分析
激酶实验	无血清培养基中的4 mL 206 nM siRNAs 加到每孔中, 0.03 mL DharmaFECT 1 在4 mL 无血清培养基中混合，加到每孔中，随后在室温下温育30分钟，形成脂质/siRNA复合体。然后25 mL完全培养基中的1.5×10³ 细胞上样到siRNA-脂质复合体的顶端。每组反应的siRNA终浓度为 25 nM。细胞在37^oC，含5% CO₂ 环境下温育。siRNA转染24小时后, 每孔中加入5 mL RAF265，使RAF265 终浓度变为0.4 mM。RAF265处理72小时后，通过CellTiter-Glo(CTG) 检测实验分析细胞活力，使用Envision获得实验数据。
细胞实验	细胞系	A375M 人黑色素瘤细胞, 表达^V600EBRAF; MV4;11人急性髓细胞性白血病细胞,表达野生型 B-Raf
	浓度	0.1 到20 µM
	孵育时间	72小时
	方法	5×10⁴A375M 或MV4;11细胞接种在24孔板中过夜。更换培养基后, 在孔中加入1.0 µM RAF265, 0.1 µM RAF265, 或无药剂(溶剂对照组)，重复三次，温育 4到 5小时和24到28小时。加入 1 µCi FDG，温育2小时。使用冷PBS冲洗细胞，然后使用 1 N NaOH溶解。使用Cobra II γ射线计数器测定一半样本放射性。通过Bradford蛋白检测实验，使用剩余样本测定蛋白浓度。在完全培养基中稀释的RAF265，浓度为0.1 到20 µM，在96孔板中和细胞温育，然后进行细胞增殖检测实验。温育72小时后，清洗细胞，进行CellTiter-Glo检测。

体内研究(In Vivo)
体内研究活性	RAF265 作用于A375M移植瘤，抑制 FDG累积。RAF265是新型，口服的小分子BRAF激酶和VEGFR-2抑制剂，作用于突变BRAF肿瘤模型，具有有效的抗癌活性。 ^[1]在人类移植瘤研究中, RAF265作用于突变BRAF人移植瘤和一些野生型BRAF模型，都具有高效性。^[4]
动物实验	Animal Models	45只皮下注射3百万A375M细胞的8周大的雌性nu/nu小鼠
	Dosages	100 mg/kg(体积约为 100 µL)
	Administration	口服处理，每两天处理一次，持续14天。

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT01352273	Completed	Advanced Solid Tumors	Array Biopharma now a wholly owned subsidiary of Pfizer\|Array BioPharma	June 2011	Phase 1

参考文献
[1] AACR Meeting Abstracts 2008;2008:4876. [2] Mordant P, et al. Mol Cancer Ther, 2010, 9(2), 358-368. [3] Zitzmann K, et al. Endocr Relat Cancer, 2011, 18(2), 277-285. [4] Chen J, et al. Cancer Res, 2011, 71(12), 4280-4291. [5] Tseng JR, et al. Neoplasia, 2011, 13(3), 266-275. + 展开

参考文献

+ 展开

化学信息&溶解度

分子量	518.41	分子式	C₂₄H₁₆F₆N₆O
CAS号	927880-90-8	SDF	Download RAF265 (CHIR-265) SDF
Smiles	CN1C2=C(C=C(C=C2)OC3=CC(=NC=C3)C4=NC=C(N4)C(F)(F)F)N=C1NC5=CC=C(C=C5)C(F)(F)F
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

DMSO : 100 mg/mL ( (192.89 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 45 mg/mL (86.8 mM)

Water : Insoluble

DMSO : 100 mg/mL ( (192.89 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 50 mg/mL (96.44 mM)

Water : Insoluble

摩尔浓度计算器

体内溶解度
批次：

现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

动物体内配方计算器（澄清溶液）

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

计算结果：

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH₂O，混匀澄清。

体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。

注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

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