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
CAS: 879085-55-9
产品质控
批次：
纯度：
99.99%
99.99
Vismodegib (GDC-0449)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 |
|---|---|---|---|---|---|
| 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。 | ||
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| 靶点 |
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| 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，且作用于肺癌细胞， 抑制细胞生长。[3] |
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| 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。 |
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| 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 |
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22087285 | |
| Immunofluorescence | Gli1 / Gli2 |
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22087285 | |
| Growth inhibition assay | Cell viability |
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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 |
|---|---|---|---|---|---|
| NCT06344052 | Recruiting | Basal Cell Carcinoma |
Stamford Pharmaceuticals Inc. |
April 9 2024 | Phase 2 |
| 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 |
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 |
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 |
|
体内溶解配方 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
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
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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