Regorafenib

别名: Fluoro-Sorafenib, BAY 73-4506 中文名称:

Regorafenib是一个多靶点抑制剂,作用于VEGFR1VEGFR2VEGFR3PDGFR-βKit (c-Kit)RET (c-RET)Raf-1,在无细胞试验中IC50分别是13 nM,4.2 nM,46 nM,22 nM,7 nM,1.5 nM和2.5 nM。Regorafenib 可诱导自噬。

Regorafenib Chemical Structure

Regorafenib Chemical Structure

CAS: 755037-03-7

规格 价格 库存 购买数量
10mM (1mL in DMSO) 794.43 现货
5mg 647.01 现货
25mg 1941.03 现货
100mg 4823.91 现货
1g 7944.3 现货
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Regorafenib相关产品

相关信号通路图

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
Hct-116 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
HT-29 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
DLD1 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
HT15 Growth Inhibition Assay 1-20 μM 48 h inhibits cell growth in a dose-dependent manner 25071018
MDA-MB-231 Function Assay 0.5/5 μM 24 h inhibits the cell migration 25253994
MCF-7 Function Assay 0.5/5 μM 24 h inhibits the cell migration 25253994
RJ348 Function Assay 0.5/5 μM 24 h inhibits the cell migration 25253994
RJ345 Function Assay 0.5/5 μM 24 h inhibits the cell migration 25253994
GEO-CR Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
SW48-CR Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
HCT150 Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
LOVO Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
HCT116 Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
SW620 Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
SW480 Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
HT29 Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
SW48 Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
GEO Growth Inhibition Assay 0.01-20 μM 96 h inhibits cell growth in a dose-dependent manner 25838391
HEK293 Function Assay 0.5 μM 2/4/6 h reduces GRP78 expression 25858032
HepG2  Apoptosis Assay 1–5 μM 48 h inhibits cell growth 26329608
PLC/PRF/5  Apoptosis Assay 1–5 μM 48 h inhibits cell growth 26329608
Hep3B Apoptosis Assay 1–5 μM 48 h inhibits cell growth 26329608
HT15 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
DLD1 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
HT-29 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
Hct-116 Apoptosis Assay 1-10 μM 48 h induces cell death in a dose-dependent manner 25071018
GBM5 Apoptosis Assay 0.5–1.0 μM 24 h interacts with lapatinib to induce cell death 24911215
GBM6 Apoptosis Assay 0.5–1.0 μM 24 h interacts with lapatinib to induce cell death 24911215
GBM12 Apoptosis Assay 0.5–1.0 μM 24 h interacts with lapatinib to induce cell death 24911215
GBM14  Apoptosis Assay 0.5–1.0 μM 24 h interacts with lapatinib to induce cell death 24911215
Hep3B Growth Inhibition Assay 1–2.5 μM 24/48/72 h inhibits cell growth 24885890
PLC/PRF/5  Growth Inhibition Assay 1–2.5 μM 24/48/72 h inhibits cell growth 24885890
HepG2  Growth Inhibition Assay 1–2.5 μM 24/48/72 h inhibits cell growth 24885890
HCT116  Function Assay 10/20/40 μM 24 h induces PUMA protein and mRNA expression in a dose- and time-dependent manner 24763611
Lim2405 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
LoVo Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
Lim1215 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW48 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
RKO  Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW837 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW1463 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
SW480 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
Vaco432 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
Vaco400 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
DLD1 Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
HT29  Function Assay 40 μM 24 h induces PUMA protein and cell apoptosis 24763611
PLC/PRF/5  Growth Inhibition Assay 1–5µM 24/48/72 h inhibits cell growth 23169148
HepG2 Growth Inhibition Assay 1–5µM 24/48/72 h inhibits cell growth 23169148
Hep3B  Growth Inhibition Assay 1–5µM 24/48/72 h inhibits cell growth 23169148
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.021 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.029 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.033 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.047 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.049 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.051 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.063 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.094 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.108 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.114 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.114 μM. 30204441
GISTT1 Cytotoxicity assay 72 hrs Cytotoxicity against human GISTT1 cells assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 0.13 μM. 28991465
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.231 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.29 μM. 30204441
GISTT1 Cytotoxicity assay 72 hrs Cytotoxicity against human GISTT1 cells harboring KIT T670I mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 0.38 μM. 28991465
BA/F3 Growth inhibition assay 72 hrs Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.522 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.549 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.833 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.834 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.943 μM. 30204441
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 1.27 μM. 30204441
GISTT1 Cytotoxicity assay 72 hrs Cytotoxicity against human GISTT1 cells harboring KIT D816E mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 1.35 μM. 28991465
BA/F3 Growth inhibition assay 72 hrs Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 2.371 μM. 30204441
GIST430 Cytotoxicity assay 72 hrs Cytotoxicity against human GIST430 cells harboring KIT V654A mutant assessed as cell growth inhibition after 72 hrs by CellTiterGlo assay, GI50 = 3 μM. 28991465
BA/F3 Cytotoxicity assay 72 hrs Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 9.953 μM. 30204441
HROC46 Growth Inhibition Assay IC50=2.4 μM 25309914
HROC43 Growth Inhibition Assay IC50=5.3 μM 25309914
HROC24 Growth Inhibition Assay IC50=4.6 μM 25309914
HROC18 Growth Inhibition Assay IC50=1.3 μM 25309914
HEK293/OATP1B1 Growth Inhibition Assay IC50=6.2±0.3 nM 25753361
HEK293 Growth Inhibition Assay IC50=11.0±1.2 nM 25753361
LLC-PK1/MRP2 Growth Inhibition Assay IC50=82.4±2.7 nM 25753361
LLC-PK1 Growth Inhibition Assay IC50=42.0±3.2 nM 25753361
KB-G2 Growth Inhibition Assay IC50=9.1±0.1 nM 25753361
KB-31 Growth Inhibition Assay IC50=5.5±0.3 nM 25753361
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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 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
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
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
点击查看更多细胞系数据

生物活性

产品描述 Regorafenib是一个多靶点抑制剂,作用于VEGFR1VEGFR2VEGFR3PDGFR-βKit (c-Kit)RET (c-RET)Raf-1,在无细胞试验中IC50分别是13 nM,4.2 nM,46 nM,22 nM,7 nM,1.5 nM和2.5 nM。Regorafenib 可诱导自噬。
特性 Regorafenib是一个新的口服多激酶抑制剂。
靶点
RET [1]
(Cell-free assay)
Raf-1 [1]
(Cell-free assay)
VEGFR2 [1]
(Cell-free assay)
Kit [1]
(Cell-free assay)
VEGFR1 [1]
(Cell-free assay)
点击更多
1.5 nM 2.5 nM 4.2 nM 7 nM 13 nM
体外研究(In Vitro)
体外研究活性

在 NIH-3T3细胞中 Regorafenib 强烈抑制 VEGFR2的 自磷酸化, IC50 为3 nM. 在HAoSMCs中, Regorafenib 抑制 PDGFR-β经过PDGF-BB刺激后的自磷酸化, IC50 为90 nM. 在MCF-7 乳腺癌细胞中, Regorafenib 也会抑制FGF10刺激后 FGFR 的信号传导. Regorafenib 非常有效的抑制KITK642E 和 RETC634W这两个突变的受体, IC50 分别是大约 20 nM 和 10 nM。 Regorafenib 抑制经过VEGF165 刺激后的 HUVECs细胞的增值, IC50 为 大约 3 nM. Regorafenib抑制 FGF2刺激后的 HUVECs和PDGF-BB刺激后的HAoSMCs细胞的增殖, IC50分别是127 nM 和 146 nM [1]。 Regorafenib通过抑制酪氨酸激酶受体(VEGFR, KIT, RET, FGFR和 PDGFR)和丝氨酸/ 苏氨酸激酶受体(RAF 和 p38MAPK)来靶向作用于肿瘤细胞增殖和肿瘤脉管系统[2]。Regorafenib以浓度依赖和时间依赖方式抑制 人Hep3B, PLC/PRF/5 和 HepG2 细胞的生长[3]

激酶实验 激酶活性测定
体外激酶实验用重组的VEGFR2 (鼠源, aa785–aa1367), VEGFR3 (鼠源 aa818–aa1363), PDGFR-β (aa561–aa1106), RAF-1 (aa305–aa648) 和 BRAFV600E (aa409–aa765)的激酶活性区域进行。初始的激酶抑制反应将Regorafenib的浓度固定为1 μM. IC50的值根据选定的相应的激酶来测定, 如VEGFR1 和 RET. TIE2 的激酶抑制效果采用均相时间分辨荧光分析法测定,利用重组的TIE2细胞内区域的GST融合蛋白和生物素化的-Ahx-EPKDDAYPLYSDFG多肽作为底物。
细胞实验 细胞系 GIST 882 和 TT 细胞
浓度 5 nM-10 μM
孵育时间 96 小时
方法

为了分析细胞增殖情况, 将GIST 882 和 TT 细胞培养在含有L-glutamine谷氨酸的RPMI 培养基中,MDA-MB-231, HepG2和A375 细胞培养在含有10% hiFBS 的 DMEM 培养基中。将细胞用胰酶消化, 按5× 104 个每孔接种在96孔板中并在含有10% FBS 的完全培养基中37°C培养过夜。第二天, 将对照和Regorafenib用培养基稀释成从10 μM 到5 nM的连续终浓度, 加入 0.2% DMSO,加入细胞培养基中并继续培养96小时。将细胞增殖情况进行量化。

实验图片 检测方法 检测指标 实验图片 PMID
Western blot p-STAT3 / STAT3 / PARP / Caspase-9 Cyclin D / Cyclin E / Cyclin A / Cyclin B / p27 / p21 p-FGFR2 / p-FRS2α / p-AKT / p-MAPK / p-P90RSK / FGFR2 / AKT / MAPK / p90RSK p-p65(S536) / p65 Bim / Bid / Bak / Bcl-Xl / Mcl-1 PUMA / p53 25071018
Immunofluorescence F-actin / Vimentin / E-cadherin p65 27580057
Growth inhibition assay Cell viability GI50 25071018
体内研究(In Vivo)
体内研究活性

在多种临床前人类异种移植的小鼠模型上, Regorafenib有着很好的肿瘤生长抑制性,这种抑制具有剂量依赖特性, 表现为在乳腺 MDA-MB-231 和 肾脏 786-O 肿瘤模型中肿瘤减小. Regorafenib 不仅阻止了同源主要的 4T1乳腺肿瘤在脂肪垫中的原位生长,也抑制了肿瘤转移到肺部[1]

动物实验 Animal Models 携带Colo-205, MDA-MB-231 细胞或者 786-O肿瘤的雌性无胸腺NCr nu/nu 小鼠
Dosages 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
Administration 口服
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06321055 Not yet recruiting
Advanced Gastrointestinal Stromal Tumor
Bayer
March 20 2024 --
NCT06137170 Active not recruiting
Metastatic Colorectal Cancer
Bayer
March 1 2024 --
NCT06029010 Completed
Metastatic Colorectal Cancer
Bayer
August 31 2023 --
NCT05370807 Recruiting
Melanoma Stage III|Melanoma Stage IV
Universitair Ziekenhuis Brussel
October 3 2022 Phase 2

化学信息&溶解度

分子量 482.82 分子式

C21H15ClF4N4O3

CAS号 755037-03-7 SDF Download Regorafenib SDF
Smiles CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 97 mg/mL ( (200.9 mM) ;DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 5 mg/mL (10.35 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

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)

mg/kg g μL

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,: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: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: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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常见问题及建议解决方法

问题 1:
How to resuspend Regorafenib for in vivo studies?

回答:
For in vivo study, we recommend to use 2% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 5mg/ml.

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