Vismodegib (GDC-0449)

For research use only. Not for use in humans.

目录号:S1082 中文名称:维莫德吉

Vismodegib (GDC-0449) Chemical Structure

CAS No. 879085-55-9

Vismodegib (GDC-0449)是一种新型有效的,特异性hedgehog抑制剂,无细胞试验中IC50为3 nM,也会抑制P-gp,IC50为3.0μM。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1179.52 现货
RMB 730.63 现货
RMB 1398.12 现货
RMB 3046.91 现货
RMB 5135.45 现货
RMB 8763.3 现货
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客户使用Selleck生产的Vismodegib (GDC-0449)发表文献121篇:

产品安全说明书

Hedgehog/Smoothened抑制剂选择性比较

生物活性

产品描述 Vismodegib (GDC-0449)是一种新型有效的,特异性hedgehog抑制剂,无细胞试验中IC50为3 nM,也会抑制P-gp,IC50为3.0μM。
靶点
Hedgehog [1]
(Cell-free assay)
3 nM
体外研究

GDC-0449有效抑制hedgehog通路,是一种新型及特定合成的小分子抑制剂,IC50为3nM。[1] GDC-0449作用于Hedgehog信号通路,阻断Hedgehog配位体,即细胞表面受体PTCH 及SMO的活性,从而阻断Hedgehog信号通路。在组织生长和修复方面,Hedgehog信号通路意义重大。Hedgehog通路信号的异常激活,及不受控制的细胞增殖,可能与Hedgehog配位体,即细胞表面受体PTCH 及SMO的突变有关。在体外,GDC-0449在不抑制胰脏细胞增殖的前提下阻止原代胰脏移植物的生长,这项结果最近已经应用到临床。GDC-0449也抑制ABCG2, P-糖蛋白, 及和MDR有关联的重要MRP1 ABC载体。GDC-0449也阻断其他多种ABC载体。ABC载体属于一个膜蛋白家族,它的过量表达和耐药性有关,这也是治疗癌症的一个重大障碍。GDC-0449强抑制两种ABC载体,ABCG2/BCRP和ABCB1/P-糖蛋白,也温和抑制ABCC1/MRP1。在ABCG2过量表达的HEK293细胞中, GDC-0449可以提高荧光ABCG2底物BODIPY-哌唑嗪的保持力,也可用米托蒽醌再次处理这些细胞,产生抗肿瘤的ABCG2底物。实验使Madin-Darby犬的肾脏细胞中过量表达P糖蛋白或者MRP1,GDC-0449 提高了钙黄绿素-AM的保持力,然后载用秋水仙素处理这些细胞。另外,用米托蒽醌,托泊替康,SN-38处理的过量表达ABCG2的人类非小细胞肺癌细胞NCI-H460/par和NCI-H460/MX20,用GDC-0449再次处理。GDC-0449 作用于ABCG2 和 Pgp 的IC50值分别为1.4μM和 3.0 μM。[2]GDC-0449 改变细胞内Ca2+ 平衡,且作用于抗cisplatin的肺癌细胞, 抑制细胞生长。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
IGROV-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3jepdKSzVyPUCuNFczPDhizszN MYPTRW5ITVJ?
HCE-T MmCwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnP3TWM2OD1zLkOyNlQ4KM7:TR?= Mo\nV2FPT0WU
D-542MG MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDBZ4RKSzVyPUGuPFY4OzdizszN M{KzTnNCVkeHUh?=
23132-87 NWPYZ|VGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1LHbmlEPTB;ND60NFE1PyEQvF2= M1XsfHNCVkeHUh?=
HDLM-2 Ml;ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmS5TWM2OD16LkC0O|Y3KM7:TR?= MnjkV2FPT0WU
ACN NW\FVIw2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnZTWM2OD16LkWwNVA6KM7:TR?= Mo\GV2FPT0WU
HuO-3N1 MlXsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHrQU|NKSzVyPUmuOlAyODhizszN MlrNV2FPT0WU
BHT-101 NHS2N3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDTTWM2OD1zMT6zPEDPxE1? M{PKPHNCVkeHUh?=
KYSE-150 M{SyPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLnTWM2OD1zMT61PFQyKM7:TR?= Mme3V2FPT0WU
MC-IXC NX7KW5VkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULpeXM3UUN3ME2xNk4zOjl{IN88US=> MlraV2FPT0WU
D-423MG MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUi0Ro8yUUN3ME2xNk44PjV5IN88US=> NVzLPGJRW0GQR1XS
NY M{D6SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2\yb2lEPTB;MUSuPFkxOyEQvF2= M1XpdHNCVkeHUh?=
HOS M3T2fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7reYU{UUN3ME2xOU43PzF7IN88US=> MVXTRW5ITVJ?
NB7 MojKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NU\NTHZvUUN3ME2xOU45QTFizszN M1\PdXNCVkeHUh?=
DMS-273 MkTES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlrZTWM2OD1zNj62O|E{KM7:TR?= M33IUnNCVkeHUh?=
MDA-MB-361 NFG1PXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTF5LkK3NVEh|ryP NIDnZ2tUSU6JRWK=
DU-145 NXqxcotUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYC5fpdKUUN3ME2xPE4{OiEQvF2= NX7jTXBIW0GQR1XS
NCI-H82 NETWepZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWnJR|UxRTF7LkizPFYh|ryP MWjTRW5ITVJ?
NCI-SNU-1 M4qwW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\xdnZKSzVyPUKwMlAyQTZizszN M{C2[XNCVkeHUh?=
GCT MnnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTwW4o5UUN3ME2yNE45QDJ2IN88US=> NVW0UmtSW0GQR1XS
C2BBe1 NWmwXItlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfWSotHUUN3ME2yNU4yODV6IN88US=> NHHVWldUSU6JRWK=
LB2241-RCC MkHuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWrJR|UxRTJzLki0OFEh|ryP NGG2O4ZUSU6JRWK=
COLO-829 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPidVVVUUN3ME2yNk4yQDdzIN88US=> MlvrV2FPT0WU
EW-11 Ml[3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYW0NZQ1UUN3ME2yNk45ODJ{IN88US=> M3;y[nNCVkeHUh?=
NCI-H526 NUT6XYRzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGjDTHVKSzVyPUKzMlQ4OTdizszN MoTjV2FPT0WU
SF295 MknVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUPJR|UxRTJ2LkCyOVIh|ryP NHrycnZUSU6JRWK=
D-566MG M{\rdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGC1VlRKSzVyPUK1MlI6PDNizszN M373PHNCVkeHUh?=
8505C MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTJ3Lk[zN|Eh|ryP M4nHZ3NCVkeHUh?=
HT-29 MnThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TNc2lEPTB;Mk[uNFQ{OSEQvF2= M1jlWXNCVkeHUh?=
NBsusSR NY[x[WtrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{K0b2lEPTB;Mk[uPFAxPiEQvF2= MmPmV2FPT0WU
BV-173 NIjJbGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3v5WmlEPTB;MkiuN|E5OiEQvF2= NV;KZlltW0GQR1XS
CTB-1 MmLUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnsenBKSzVyPUOwMlExOzFizszN NV6weVh[W0GQR1XS
JAR MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjmTFRKSzVyPUOyMlU{PzFizszN M2foNnNCVkeHUh?=
CAMA-1 MoCwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVi0VVlVUUN3ME2zN{41PjF3IN88US=> NETVbIJUSU6JRWK=
CAL-51 MkfUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MorQTWM2OD1|ND63NVc3KM7:TR?= NWXqXlJtW0GQR1XS
A172 MmTWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHj3PY1KSzVyPUO3MlQ6OjFizszN MWjTRW5ITVJ?
QIMR-WIL M2Xa[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGL3Oo5KSzVyPUO4MlA4ODhizszN MmHsV2FPT0WU
AsPC-1 MoHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUXO[m5kUUN3ME2zPE41PjVzIN88US=> NFHvfFRUSU6JRWK=
MKN7 M2j0Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTN7LkCwO|kh|ryP Moj2V2FPT0WU
ONS-76 M3nINmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV;JR|UxRTR|LkOwOVch|ryP M2HPW3NCVkeHUh?=
RS4-11 NXvHNFdXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPWfm5KSzVyPUS0MlA4PTJizszN NYDmUG02W0GQR1XS
NOS-1 MnHVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHX2XlZKSzVyPUS0MlYxOzFizszN M2jufnNCVkeHUh?=
A101D MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jTW2lEPTB;NESuPFAzOyEQvF2= NWX6[HVnW0GQR1XS
HCC1806 M{fNWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjyVYlXUUN3ME20Ok4yOTR6IN88US=> M172WXNCVkeHUh?=
CAL-27 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX:5eWNYUUN3ME20O{44OjR4IN88US=> MXvTRW5ITVJ?
BT-549 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYnJR|UxRTR6LkWzNVUh|ryP NFKzZlVUSU6JRWK=
LCLC-97TM1 MnXlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPWdGdKSzVyPUS5MlI1OTNizszN MojKV2FPT0WU
A4-Fuk Mn7OS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nKSWlEPTB;NEmuPFQ6KM7:TR?= M3[yXHNCVkeHUh?=
OVCAR-4 NETTO2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTVyLkC2NFEh|ryP MorPV2FPT0WU
HD-MY-Z NGnh[|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUjhbGdCUUN3ME21NE44PzZ2IN88US=> NYj4b|d[W0GQR1XS
NCI-H292 NFnH[ZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTVyLki3OVgh|ryP NFXwe2FUSU6JRWK=
Sk-ChA-1  MlLWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\PflFCOC5{NfMAl|UxKM7:TR?= Ml;hO|IhcA>? MkH3TWM2OD15ND61OOKyOi53ON88US=> M{XBSFI2PzR{NEiy
Mz-ChA-1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3hNVUxNjJ34pETOVAh|ryP NHLuTno4OiCq NEDwUm9KSzVyPUW0Mlk4yrF|LkS1{txO MUSyOVc1OjR6Mh?=
Smo-WT NXeySlhTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxyqCxZjCxOOKhdk1? NXzMSoQ1OjR{OUGxNFQ>
Smo-D473H  NHvLWmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4f5V2lEPTEEoH;mJFcvOcLizszN Ml2zNlQzQTFzMES=
K562 NXzKbYI{TnWwY4Tpc44hSXO|YYm= MUSxNEDPxE1? MmLWO|IhcA>? Mnz6doVlfWOnczD0bIUh\XiycnXzd4lwdiCxZjDHcIkyyqB? MYOyN|MyQTh{NB?=
T315I BCR-ABL BaF3 NHWwfW5HfW6ldHnvckBCe3OjeR?= NY\VVnJHOTBizszN MlGxO|IhcA>? MoDKdoVlfWOnczD0bIUh\XiycnXzd4lwdiCxZjDHcIkyyqB? NWntXndlOjN|MUm4NlQ>
TF-1 BCR-ABL MmruSpVv[3Srb36gRZN{[Xl? M1;pcFExKM7:TR?= Mn3CO|IhcA>? MVry[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:oIFfsbVHDqA>? NHTnUm0zOzNzOUiyOC=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Fas / DR4 / DR5 / Cleaved PARP / Bcl-2 / Cleaved caspase-3 / PDGFRα; 

PubMed: 22087285     


Pancreatic CSCs were treated with GDC-0449 (0, 1, 5 and 10 µM) for 48 h. The expression of Fas, DR4/TRAIL-R1, DR5/TRAIL-R2, PARP cleavage, Bcl-2, and Caspase-3 by the Western blot analysis. β-Actin was used as a loading control.

p-GSK3β / GSK3β / p-Akt / Akt / Gli1; 

PubMed: 27143997     


Cells were pretreated with or without 30 μM GDC-0449 for 2 h before TMT treatment. After incubation with 3.75 μM TMT for another 24 h, the expression levels of proteins were determined through Western blot analysis.

Gli1 / SOX2 / OCT4; 

PubMed: 26418365     


The activation of Hedgehog pathways and CSC markers were tested by immunoblotting analysis in Hs578T and BT549 cells. β‐Actin was used as a loading control.

p53 / Cyclin D1 / p21; 

PubMed: 28195165     


GDC-0449 treatment affected the expression levels of cell cycle-related protein levels. U251 cells were treated with 0.1% DMSO or GDC-0449 at the indicated concentrations for 24 h. Cells were then harvested and examined using Western blot analysis with the indicated antibodies.

Bcl-2 / Bax; 

PubMed: 28195165     


GDC-0449 treatment affected the expression levels of cell cycle-related protein levels. U251 cells were treated with 0.1% DMSO or GDC-0449 at the indicated concentrations for 24 h. Cells were then harvested and examined using Western blot analysis with the indicated antibodies.

22087285 27143997 26418365 28195165
Immunofluorescence
Gli1 / Gli2; 

PubMed: 22087285     


GDC-0449 inhibits expression of Gli1 and Gli2 in human pancreatic CSCs. The cells were seeded on fibronectin-coated coverslips and treated with GDC-0449 (10 µM) for 48 h. Subsequently, cells were fixed with 4% paraformaldehyde, blocked in 10% normal goat serum and stained with Gli1 and Gli2 primary antibodies (1∶100) for 16 h at 4°C and washed with PBS. Afterwards, cells were incubated with fluorescently labeled secondary antibody (1∶200) along with DAPI (1 mg/ml) for 1 h at room temperature and cells were mounted and visualized under a fluorescent microscope. For better visuality, the color of DAPI was changed from blue to red.

22087285
Growth inhibition assay
Cell viability; 

PubMed: 29042665     


GDC-0449 improves the anti-proliferation activity in NIH-3T3 cells but not in BxPC-3, Panc-1, MIAPaca-2 and SW1990 cells when cultured alone. The cytotoxicities of GDC-0449, Dox or Dox with GDC-0449 (5 μM or 10 μM) were measured by performing a 48-h MTT assay in BxPC-3 (A), Panc-1 (B), MIAPaca-2 (C), SW1990 (D) and NIH-3T3 (E) cells. Apoptosis rate was detected by flow cytometry (Annexin V staining) analysis after treatment with Dox (200 nM) with or without GDC-0449 for 24 h (F). Data are presented as the mean ± SD. *P < 0.05, **P < 0.01.

29042665
体内研究 GDC-0449已经用于治疗动物模型的成髓细胞瘤。[2] GDC-0449 抑制原代胰腺移植瘤生长,但是不抑制细胞增殖。GDC-0449按25 mg/kg 以上剂量口服给药髓母细胞瘤Ptch(+/-)异体移植物模型,引起细胞衰退,按92 mg/kg剂量处理两种配位体依赖的结肠直肠癌模型D5123和1040830,每天处理两次,抑制肿瘤生长。分析Hh通路活性和 PK/PD 模型显示GDC-0449抑制 Gli1,IC50值与GDC-0449作用于髓母细胞瘤和D5123模型的IC50值差不多(分别为0.165 μM ±11.5% 和0.267 μM ±4.83%)。[4]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

细胞实验:[2]
- 合并
  • Cell lines: MDCKII细胞
  • Concentrations: 20 μM
  • Incubation Time: 2小时
  • Method: MDCKII细胞按每孔3x105密度接种在24孔板中。培养液包含不同药物,实验组为50 µM VP,50 µM吲哚美辛,或者20 µM GDC-0449溶解在DMSO中,对照组只含有DMSO。然后加入非荧光的钙黄绿素-AM,最终浓度达到1.0 µM。然后在37oC温育2小时。细胞用含Ca2+,Mg2+的Hank's平衡盐溶液buffer冲洗2次,然后震荡1小时溶解在含0.01% Triton X-100的磷酸缓冲液中,然后放在4oC下过夜。溶解的物质然后转移到96孔板上,钙黄绿素引起的荧光信号用分光光度法定量。所有的实验操作需在暗中进行,所有的读数用平均值±SEM表示。
    (Only for Reference)
动物实验:[4]
- 合并
  • Animal Models: Ptch(+/-)异体移植物模型
  • Dosages: 25 mg/kg,92 mg/kg
  • Administration: 口服
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 84 mg/mL (199.38 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
5% DMSO+40% PEG 300+5% Tween 80+50% ddH2O
12.5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 421.3
化学式

C19H14Cl2N2O3S

CAS号 879085-55-9
储存条件 粉状
溶于溶剂
别名 N/A

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 ul 动物数量
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
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03610022 Recruiting Drug: Treatment with vismodegib Metastatic Basal Cell Carcinoma|Locally Advanced Basal Cell Carcinoma University Hospital Bordeaux September 3 2018 Phase 4
NCT03035188 Active not recruiting Drug: Vismodegib Basal Cell Carcinoma SRH Wald-Klinikum Gera GmbH January 2017 Phase 2
NCT02781389 Active not recruiting -- Basal Cell Carcinoma University Hospital Essen|OnkoDataMed GmbH April 29 2016 --
NCT02593760 Completed Other: Placebo|Drug: Ruxolitinib|Drug: Vismodegib Myelofibrosis Hoffmann-La Roche January 25 2016 Phase 1
NCT02648048 Completed Drug: Pirfenidone|Drug: Vismodegib Idiopathic Pulmonary Fibrosis Hoffmann-La Roche January 15 2016 Phase 1
NCT02366312 Completed Drug: vismodegib Keratocystic Odontogenic Tumor NYU College of Dentistry|Genentech Inc. October 27 2015 Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID