Vismodegib (GDC-0449)

别名: GDC-0449 中文名称:维莫德吉

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。

Vismodegib (GDC-0449) Chemical Structure

Vismodegib (GDC-0449) Chemical Structure

CAS: 879085-55-9

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1179.52 现货
5mg RMB 730.63 现货
50mg RMB 3046.91 现货
200mg RMB 7944.3 现货
1g RMB 16134.3 现货
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客户使用Selleck的Vismodegib (GDC-0449)发表文献197

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批次: 纯度: 99.99%
99.95

Vismodegib (GDC-0449)相关产品

Hedgehog/Smoothened抑制剂选择性比较

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
Sk-ChA-1  Growth Inhibition Assay 0.25–50 μM 72 h IC50=74.54±2.58μM 25742482
Mz-ChA-1 Growth Inhibition Assay 0.25–50 μM 72 h IC50=54.97±3.45μM 25742482
K562 Function Assay 10 μM 72 h reduces the expression of Gli1  23319824
T315I BCR-ABL BaF3 Function Assay 10 μM 72 h reduces the expression of Gli1  23319824
TF-1 BCR-ABL Function Assay 10 μM 72 h reduces the expression of Gli1  23319824
Shh Light2 Function assay 0.1 uM 36 hrs Inhibition of Smo-mediated Hh signalling pathway in mouse Shh Light2 cells assessed as suppression of Gli1-mRNA expression at 0.1 uM measured after 36 hrs by RT-qPCR analysis. 27736063
SW1353 Antiproliferative assay 10 uM 48 hrs Antiproliferative activity against human SW1353 cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay. 24491459
DaOY Antiproliferative assay 10 uM 48 hrs Antiproliferative activity against human DaOY cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay. 24491459
A549 Antiproliferative assay 10 uM 48 hrs Antiproliferative activity against human A549 cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay. 24491459
HCT116 Antiproliferative assay 10 uM 48 hrs Antiproliferative activity against human HCT116 cells assessed as growth inhibition at 10 uM after 48 hrs by MTT assay. 24491459
NIH3T3-Luc Function assay 1 uM 48 hrs Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3-Luc cells assessed as downregulation of Gli mRNA expression at 1 uM after 48 hrs by real-time PCR analysis. 29499483
NIH/3T3 Function assay 100 nM 36 hrs Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as downregulation of Shh-induced Gli1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis. 28873303
C3H10T1/2 Function assay 100 nM 36 hrs Inhibition of hedgehog signaling pathway in mouse C3H10T1/2 cells assessed as downregulation of Shh-induced Gli1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis. 28873303
NIH/3T3 Function assay 100 nM 36 hrs Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as downregulation of Shh-induced ptch1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis. 28873303
C3H10T1/2 Function assay 100 nM 36 hrs Inhibition of hedgehog signaling pathway in mouse C3H10T1/2 cells assessed as downregulation of Shh-induced ptch1 mRNA expression levels at 100 nM after 36 hrs by RT-qPCR analysis. 28873303
medulloblastoma cell Antiproliferative assay up to 30 uM 72 hrs Antiproliferative activity against mouse Ptch+/- p53-/- medulloblastoma cells assessed as reduction in cell proliferation up to 30 uM after 72 hrs by MTS assay. 28873303
NIH/3T3 Function assay 10 uM Inhibition of Hedgehog signaling in mouse NIH/3T3 cells assessed as down regulation of mPTCH1 mRNA expression at 10 uM. 24491459
MSC Function assay 20 to 80 uM Inhibition of hedgehog signaling in mouse MSC cells assessed as down regulation of alkaline phosphatase at 20 to 80 uM. 24491459
C3H10T1/2 Function assay 4.1 to 1000 nM Allosteric inhibition of Smo in mouse C3H10T1/2 cells assessed as inhibition of purmorphamine-induced Gli1 transcriptional activity at 4.1 to 1000 nM by qPCr analysis. 23074541
C3H10T1/2 Function assay 4.1 to 1000 nM Competitive inhibition of Smo in mouse C3H10T1/2 cells assessed as inhibition of SAG-induced Gli1 transcriptional activity at 4.1 to 1000 nM by qPCR analysis. 23074541
Shh-Light 2 Function assay 2 days Antagonist activity at Smo in mouse Shh-Light 2 cells assessed as inhibition of Shh-induced Gli1-reporter activity after 2 days by dual-luciferase reporter gene method, IC50 = 0.0015 μM. 23063522
Light2 Function assay 48 hrs Inhibition of hedgehog signaling pathway in mouse Light2 cells after 48 hrs by Gli-luciferase reporter gene assay, IC50 = 0.00246 μM. 29739714
C3H10T1/2 Function assay 20 hrs Inhibition of Smo in mouse C3H10T1/2 cells using human recombinant SHH assessed as effect on SMO/SHH transient transcriptional activation after 20 hrs by Gli-luciferase reporter assay, IC50 = 0.005 μM. 24900436
NIH/3T3 Function assay 24 hrs Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells measured after 24 hrs by Gli-dual luciferase reporter gene assay, IC50 = 0.005 μM. 27810591
NIH3T3 Function assay 48 hrs Inhibition of smo-mediated hedgehog signaling pathway in mouse NIH3T3 cells expressing GRE-Luc reporter gene assessed as inhibition of SAG-induced GRE-Luc reporter activity after 48 hrs by luminescence assay, IC50 = 0.006 μM. 29499483
HEK293 Function assay 2 hrs Displacement of BODIPY-labelled cyclopamine from human Smo receptor expressed in HEK293 cells after 2 hrs by fluorescence microscopy, IC50 = 0.007 μM. 22268551
NIH/3T3 Function assay 48 hrs Inhibition of Hedgehog signaling pathway in mouse NIH/3T3 cells assessed as reduction in Sonic hedgehog-induced Gli luciferase activity after 48 hrs by Dual-luciferase reporter gene assay, IC50 = 0.00717 μM. 30249494
NIH3T3 Function assay 48 hrs Inhibition of hedgehog signalling in mouse NIH3T3 cells stably transfected with Gli-luciferase construct incubated for 48 hrs by dual luciferase reporter gene assay, IC50 = 0.0072 μM. 26827136
NIH3T3 Function assay 48 hrs Inhibition of Sonic-induced hedgehog signalling in mouse NIH3T3 cells after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0072 μM. 26820554
NIH3T3 Function assay 48 hrs Inhibition of SHH signaling pathway in mouse NIH3T3 cells measured after 48 hrs by Gli-luciferase reporter assay, IC50 = 0.0072 μM. 24176396
NIH/3T3 Function assay 48 hrs Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells after 48 hrs by Gli-luciferase reporter gene assay, IC50 = 0.0072 μM. 24486203
C3H10T1/2 Function assay 6 hrs Inhibition of SAG-induced differentiation of mouse mesenchymal pluripotent C3H10T1/2 cells to alkaline phosphatase positive oeseoblasts after 6 hrs, IC50 = 0.011 μM. 22268551
TM3 Function assay 48 hrs Inhibition of Hh signaling pathway in mouse TM3 cells assessed as downregulation of Gli1 gene expression after 48 hrs by luciferase reporter gene assay, EC50 = 0.013 μM. 26976215
S12 Function assay 48 hrs Inhibition of human SHH pathway in mouse S12 cells assessed as GLI-mediated transcriptional activity after 48 hrs by luciferase reporter gene assay, IC50 = 0.015 μM. 21438527
U2OS Function assay 2 hrs Displacement of [3H]cyclopamine from wild type Smo expressed in U2OS cells after 2 hrs by scintillation counting, Ki = 0.0162 μM. 23063522
NIH3T3 Function assay 30 hrs Inhibition of Smo receptor (unknown origin) expressed in NIH3T3 cells assessed as inhibition of Smo agonist SAG-induced GRE activation after 30 hrs by luciferase reporter gene assay, IC50 = 0.023 μM. 24726807
medulloblastoma cell Antiproliferative assay 36 hrs Antiproliferative activity against Ptch+/- and p53-/- mouse medulloblastoma cells after 36 hrs by Brdu incorporation assay, IC50 = 0.0304 μM. 28688278
ASZ001 Function assay 48 hrs Inhibition of Hedgehog signaling in mouse ASZ001 cells assessed as downregulation of Gli1 mRNA expression after 48 hrs by RT-PCR analysis, IC50 = 0.04 μM. 24900716
NIH/3T3 Function assay 48 hrs Antagonist activity at Smo receptor in mouse NIH/3T3 cells harboring GRE-Luc assessed as inhibition of SAG-induced Hh signaling pathway preincubated with cells followed by SAG addition measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.046 μM. 29857275
Light2 Function assay 30 hrs Inhibition of hedgehog signaling pathway in mouse Light2 cells in Shh conditioned medium after 30 hrs by Gli-Renilla luciferase reporter gene assay, IC50 = 0.05 μM. 30099257
C3H10T1/2 Function assay 6 days Inhibition of hedgehog signaling pathway-mediated differentiation of mouse C3H10T1/2 cells assessed as decrease in SAG-induced ALP activity after 6 days by chemiluminescence-based assay, IC50 = 0.05 μM. 30099257
DaOY Function assay 48 hrs Inhibition of Hedgehog signaling in human DaOY cells assessed as downregulation of Gli1 mRNA expression after 48 hrs by RT-PCR analysis, IC50 = 0.086 μM. 24900716
C3H10T1/2 Function assay 1 hr Inhibition of Hedgehog signaling pathway in mouse C3H10T1/2 cells assessed as reduction in purmorphamine-induced increase in alkaline phosphatase level using CDP-star as substrate pretreated for 1 hr followed by purmorphamine addition measured after 5 day, IC50 = 0.14 μM. 28947939
M210B4 Function assay 24 hrs Inhibition of Hedgehog signaling in mouse M210B4 cells assessed as downregulation of Ptch mRNA expression after 24 hrs by RT-PCR analysis, IC50 = 0.14 μM. 24900716
M210B4 Function assay 24 hrs Inhibition of Hedgehog signaling in mouse M210B4 cells assessed as downregulation of Gli1 mRNA expression after 24 hrs by RT-PCR analysis, IC50 = 0.2 μM. 24900716
Shh Light2 Function assay 1 hr Inhibition of Hedgehog signaling in mouse Shh Light2 cells assessed as reduction in purmorphamine-induced Gli mediated transcriptional activity pretreated for 1 hr followed by purmorphamine addition measured after 48 hrs by luciferase reporter gene assay, IC50 = 0.98 μM. 28947939
S12 Function assay 48 hrs Inhibition of human SHH pathway in mouse S12 cells assessed as GLI-mediated transcriptional activity after 48 hrs by luciferase reporter gene assay in presence of 0.5 mg/mL human alpha-1-acid glycoprotein, IC50 = 1.75 μM. 21438527
Calu6 Function assay 4 hrs Plasma concentration in human Calu6 cells xenografted in nude mouse at 75 mg/kg, po bid measured after 4 hrs post fifth dose, Cp = 23 μM. 19716296
T47D Cytotoxicity assay 72 hrs Cytotoxicity against human T47D cells after 72 hrs by MTT assay, IC50 = 41.34 μM. 29107429
LS180 Antiproliferative assay 72 hrs Antiproliferative activity against human LS180 cells after 72 hrs by sulforhodamine-B assay, IC50 = 45 μM. 30099257
LS174T Antiproliferative assay 72 hrs Antiproliferative activity against human LS174T cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 45.81 μM. 26820554
BxPC3 Antiproliferative assay 72 hrs Antiproliferative activity against human BxPC3 cells after 72 hrs by CellTiter-Glo luminescent cell viability assay, IC50 = 47.95 μM. 26820554
S12 Function assay 48 hrs Inhibition of human SHH pathway in mouse S12 cells assessed as GLI-mediated transcriptional activity after 48 hrs by luciferase reporter gene assay in presence of 1 mg/mL human alpha-1-acid glycoprotein. 21438527
C3H10T1/2 Function assay 24 hrs Inhibition of hedgehog signaling pathway-mediated GLI1 mRNA expression in mouse C3H10T1/2 cells after 24 hrs by RT-PCR analysis in presence of (1R,3aR,4S,7aR)-7a-methyl-1-((R)-6-methylheptan-2-yl)octahydro-1H-inden-4-yl 3-hydroxybenzoate. 24730984
C3H10T1/2 Function assay 24 hrs Inhibition of hedgehog signaling pathway-mediated GLI1 mRNA expression in mouse C3H10T1/2 cells after 24 hrs by RT-PCR analysis in presence of VD3. 24730984
EW-11 Growth Inhibition Assay IC50=22.8022 μM SANGER
COLO-829 Growth Inhibition Assay IC50=22.1871 μM SANGER
LB2241-RCC Growth Inhibition Assay IC50=21.8441 μM SANGER
C2BBe1 Growth Inhibition Assay IC50=21.1058 μM SANGER
GCT Growth Inhibition Assay IC50=20.8824 μM SANGER
NCI-SNU-1 Growth Inhibition Assay IC50=20.0196 μM SANGER
NCI-H82 Growth Inhibition Assay IC50=19.8386 μM SANGER
DU-145 Growth Inhibition Assay IC50=18.32 μM SANGER
MDA-MB-361 Growth Inhibition Assay IC50=17.2711 μM SANGER
DMS-273 Growth Inhibition Assay IC50=16.6713 μM SANGER
NB7 Growth Inhibition Assay IC50=15.891 μM SANGER
HOS Growth Inhibition Assay IC50=15.6719 μM SANGER
NY Growth Inhibition Assay IC50=14.8903 μM SANGER
D-423MG Growth Inhibition Assay IC50=12.7657 μM SANGER
MC-IXC Growth Inhibition Assay IC50=12.2292 μM SANGER
KYSE-150 Growth Inhibition Assay IC50=11.5841 μM SANGER
BHT-101 Growth Inhibition Assay IC50=11.38 μM SANGER
HuO-3N1 Growth Inhibition Assay IC50=9.60108 μM SANGER
ACN Growth Inhibition Assay IC50=8.50109 μM SANGER
HDLM-2 Growth Inhibition Assay IC50=8.04766 μM SANGER
23132-87 Growth Inhibition Assay IC50=4.40147 μM SANGER
D-542MG Growth Inhibition Assay IC50=1.86737 μM SANGER
HCE-T Growth Inhibition Assay IC50=1.32247 μM SANGER
IGROV-1 Growth Inhibition Assay IC50=0.07248 μM SANGER
NCI-H526 Growth Inhibition Assay IC50=23.4717 μM SANGER
SF295 Growth Inhibition Assay IC50=24.0252 μM SANGER
D-566MG Growth Inhibition Assay IC50=25.2943 μM SANGER
8505C Growth Inhibition Assay IC50=25.6331 μM SANGER
HT-29 Growth Inhibition Assay IC50=26.0431 μM SANGER
NBsusSR Growth Inhibition Assay IC50=26.8006 μM SANGER
BV-173 Growth Inhibition Assay IC50=28.3182 μM SANGER
CTB-1 Growth Inhibition Assay IC50=30.1031 μM SANGER
JAR Growth Inhibition Assay IC50=32.5371 μM SANGER
CAMA-1 Growth Inhibition Assay IC50=33.4615 μM SANGER
CAL-51 Growth Inhibition Assay IC50=34.7176 μM SANGER
A172 Growth Inhibition Assay IC50=37.4921 μM SANGER
QIMR-WIL Growth Inhibition Assay IC50=38.0708 μM SANGER
AsPC-1 Growth Inhibition Assay IC50=38.4651 μM SANGER
MKN7 Growth Inhibition Assay IC50=39.0079 μM SANGER
ONS-76 Growth Inhibition Assay IC50=43.3057 μM SANGER
RS4-11 Growth Inhibition Assay IC50=44.0752 μM SANGER
NOS-1 Growth Inhibition Assay IC50=44.6031 μM SANGER
A101D Growth Inhibition Assay IC50=44.8023 μM SANGER
HCC1806 Growth Inhibition Assay IC50=46.1148 μM SANGER
CAL-27 Growth Inhibition Assay IC50=47.7246 μM SANGER
BT-549 Growth Inhibition Assay IC50=48.5315 μM SANGER
LCLC-97TM1 Growth Inhibition Assay IC50=49.2413 μM SANGER
A4-Fuk Growth Inhibition Assay IC50=49.849 μM SANGER
OVCAR-4 Growth Inhibition Assay IC50=50.0601 μM SANGER
HD-MY-Z Growth Inhibition Assay IC50=50.7764 μM SANGER
NCI-H292 Growth Inhibition Assay IC50=50.8758 μM SANGER
Smo-WT Growth Inhibition Assay IC50 of 14 nM 24291104
Smo-D473H  Growth Inhibition Assay IC50 of 7.1 μM 24291104
NIH/3T3 Function assay Inhibition of hedgehog signaling (unknown origin) expressed in mouse NIH/3T3 cells by Gli-dual-luciferase reporter assay, IC50 = 0.0023 μM. 27180012
NIH/3T3 Light2 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 Light2 cells by Gli-luciferase reporter gene assay, IC50 = 0.0023 μM. 28688278
HEPM Function assay Inhibition of SHH in human HEPM cells by Gli-luciferase reporter gene assay, INH = 0.0028 μM. 19716296
Shh Light2 Function assay Inhibition of SHH in mouse Shh Light2 cells by GLI-responsive firefly luciferase reporter gene assay, IC50 = 0.003 μM. 19309080
HEPM Function assay Inhibition of Hedgehog signaling in human HEPM cells assessed as reduction in receptor-mediated Gli1 mRNA expression by reporter gene assay, INH = 0.003 μM. 20875741
Shh-light2 Function assay Inhibition of Smo-mediated Hh signaling in human Shh-light2 cells by luciferase reporter gene assay, IC50 = 0.007 μM. 22268551
NIH3T3 Function assay Inhibition of hedgehog receptor signaling pathway in mouse NIH3T3 cells transfected with Gli-reporter gene by luciferase reporter gene assay, IC50 = 0.00717 μM. 24923765
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells by Gli1-luciferase reporter gene assay, IC50 = 0.0072 μM. 24405704
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells carrying stably transfected Gli-reporter construct by luciferase reporter assay, IC50 = 0.0072 μM. 28642101
HCC827 Function assay Displacement of [3H]-cyclopamine from SMO V404M mutant in gefitinib resistant human HCC827 cells by scintillation counting, Ki = 0.0122 μM. 28787156
C3H10T1/2 Function assay Inhibition of SHH in mouse C3H10T1/2 cells by Gli-luciferase reporter gene assay, IC50 = 0.013 μM. 19716296
S12 Function assay Inhibition of Hedgehog signaling in mouse S12 cells assessed as reduction in receptor-mediated Gli1 mRNA expression by reporter gene assay, INH = 0.013 μM. 20875741
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells expressing wild type Smo assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 0.0144 μM. 27810591
NIH/3T3 Function assay Inhibition of SMO in mouse NIH/3T3 cells assessed as inhibition of SAG-induced hedgehog-mediated luminescence signaling by GRE-luciferase reporter gene assay, IC50 = 0.016 μM. 26119500
Shh Light2 Function assay Antagonist activity at smoothened (unknown origin) expressed in mouse Shh Light2 cells co-expressing Gli-dependent reporter gene assessed as inhibition of Hh signaling by dual luciferase reporter gene assay, IC50 = 0.033 μM. 24491459
Light2 Function assay Inhibition of hedgehog signaling pathway in mouse Light2 cells in Shh conditioned medium by Gli-luciferase reporter gene assay, IC50 = 0.039 μM. 28873303
Shh Light2 Function assay Inhibition of Smo-mediated Hh signalling pathway in mouse Shh Light2 cells by Gli-luciferase reporter gene assay, IC50 = 0.0392 μM. 27736063
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells harboring Smo D477H mutant assessed as reduction in Gli mRNA expression by RT-PCR method, IC50 = 1.196 μM. 27810591
Calu-6 Function assay Plasma concentration in Calu-6 cells xenografted nude mouse PK/PD model at 75 mg/kg, po bid for 5 days measured 4 hrs post last dose relative to untreated control, Cp = 23 μM. 20875741
medulloblastoma cell Antitumor assay Antitumor activity against mouse medulloblastoma cells xenografted in Ptch +/- mouse assessed as decrease in tumor volume at 12.5 mg/kg, po bid. 19716296
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
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells. 29435139
medulloblastoma cell Apoptosis assay Induction of apoptosis in mouse Ptch+/- p53-/- medulloblastoma cells implanted in athymic nude mouse at 12.5 mg/kg, ip bid for 15 consecutive days by TUNEL assay. 28873303
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway expressed in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Gli-2 accumulation at tip of primary cilia by DAPI staining based confocal microscopic analysis. 27810591
NIH/3T3 Function assay Inhibition of hedgehog signaling pathway in mouse NIH/3T3 cells assessed as inhibition of hedgehog-induced Smo-EGFP ciliary translocation by DAPI staining based confocal microscopic analysis. 27810591
medulloblastoma cell Anti-tumor assay Anti-tumor activity against mouse Ptch+/- p53-/- medulloblastoma cells implanted in athymic nude mouse assessed as tumor growth inhibition at 20 mg/kg, po administered twice daily via gavage measured every other day during compound dosing. 29739714
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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(In Vitro)
体外研究活性 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]
细胞实验 细胞系 MDCKII细胞
浓度 20 μM
孵育时间 2小时
方法 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。
实验图片 检测方法 检测指标 实验图片 PMID
Western blot Fas / DR4 / DR5 / Cleaved PARP / Bcl-2 / Cleaved caspase-3 / PDGFRα p-GSK3β / GSK3β / p-Akt / Akt / Gli1 Gli1 / SOX2 / OCT4 p53 / Cyclin D1 / p21 Bcl-2 / Bax 22087285
Immunofluorescence Gli1 / Gli2 22087285
Growth inhibition assay Cell viability 29042665
体内研究(In Vivo)
体内研究活性 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]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03610022 Completed
Metastatic Basal Cell Carcinoma|Locally Advanced Basal Cell Carcinoma
University Hospital Bordeaux
September 3 2018 Phase 4
NCT03035188 Completed
Basal Cell Carcinoma
SRH Wald-Klinikum Gera GmbH
January 2017 Phase 2
NCT02781389 Completed
Basal Cell Carcinoma
University Hospital Essen|OnkoDataMed GmbH
April 29 2016 --
NCT02593760 Completed
Myelofibrosis
Hoffmann-La Roche
January 25 2016 Phase 1
NCT02648048 Completed
Idiopathic Pulmonary Fibrosis
Hoffmann-La Roche
January 15 2016 Phase 1
NCT02436408 Completed
Carcinoma Basal Cell
University of Michigan Rogel Cancer Center
July 15 2015 Phase 4

化学信息&溶解度

分子量 421.3 分子式

C19H14Cl2N2O3S

CAS号 879085-55-9 SDF Download Vismodegib (GDC-0449) SDF
Smiles CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 84 mg/mL ( 199.38 mM; DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Water : Insoluble

Ethanol : 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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