Vismodegib (GDC-0449) 化学構造
分子量: 421.3

高品質保証

文献中の引用(33)

カスタマーフィードバック(15)

Quality Control & MSDS

製品説明

  • Compare Hedgehog/Smoothened Inhibitors
    Hedgehog/Smoothened製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 Vismodegib (GDC-0449)は、強力で、新しくて、特定のハリネズミ経路阻害剤で、 IC50 が 3 nMになる。
ターゲット Hedgehog
IC50 3 nM [1]
In vitro試験 GDC-0449 targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. GDC-0449 prevents multiple ATP-binding cassette (ABC) transporters. GDC-0449 also blocks ABCG2, Pgp, and MRP1-important ABC transporters associated with MDR. GDC-0449 is a potent inhibitor of ABC transporters, ABCG2/BCRP and ABCB1/Pgp, and is a mild inhibitor of ABCC1/MRP1. In ABCG2-overexpressing HEK293 cells, GDC-0449 increases retention of the fluorescent ABCG2 substrate BODIPY-prazosin and resensitizes these cells to mitoxantrone. In Madin-Darby canine kidney II cells engineered to overexpress Pgp or MRP1, GDC-0449 increases the retention of calcein-AM and resensitizes them to colchicine. GDC-0449 also resensitizes human non-small cell lung carcinoma cells NCI-H460/par and NCI-H460/MX20, which overexpress ABCG2 in response to mitoxantrone, to mitoxantrone, and to topotecan or SN-38. The IC50 values of GDC-0449 for prevention of ABCG2 and Pgp are about 1.4 μM and 3.0 μM, respectively. [2] GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. [3]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
IGROV-1 M3HjZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkfBTWM2OD1yLkC3NlQ5KM7:TR?= NHOyVphUSU6JRWK=
HCE-T NGHIZppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M375Z2lEPTB;MT6zNlI1PyEQvF2= MlH2V2FPT0WU
D-542MG MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7vTWM2OD1zLki2O|M4KM7:TR?= MnfxV2FPT0WU
23132-87 M3rFSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M37ORWlEPTB;ND60NFE1PyEQvF2= MWfTRW5ITVJ?
HDLM-2 MonhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHNTWM2OD16LkC0O|Y3KM7:TR?= MWTTRW5ITVJ?
ACN NX\zTZVkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2myWGlEPTB;OD61NFExQSEQvF2= NYfIR|U1W0GQR1XS
HuO-3N1 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFG3RpdKSzVyPUmuOlAyODhizszN MWjTRW5ITVJ?
BHT-101 NV7h[5hpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXyydodOUUN3ME2xNU4{QCEQvF2= MniyV2FPT0WU
KYSE-150 NUD3fZlRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfVSItKSzVyPUGxMlU5PDFizszN M1W0W3NCVkeHUh?=
MC-IXC MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHmRXhbUUN3ME2xNk4zOjl{IN88US=> MXXTRW5ITVJ?
D-423MG NXflOo1uT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MojOTWM2OD1zMj63OlU4KM7:TR?= MnzjV2FPT0WU
NY MlXYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnmTWM2OD1zND64PVA{KM7:TR?= MnLMV2FPT0WU
HOS M2n0N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYn0[Yt5UUN3ME2xOU43PzF7IN88US=> MX7TRW5ITVJ?
NB7 M{ftd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLOTWM2OD1zNT64PVEh|ryP M1S1XHNCVkeHUh?=
DMS-273 NVvXV3dsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUfJR|UxRTF4Lk[3NVMh|ryP MYnTRW5ITVJ?
MDA-MB-361 Mlf6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPkTWM2OD1zNz6yO|EyKM7:TR?= NEHHNldUSU6JRWK=
DU-145 NHX1PXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{ThW2lEPTB;MUiuN|Ih|ryP NE\1eJNUSU6JRWK=
NCI-H82 Mn3lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PSOGlEPTB;MUmuPFM5PiEQvF2= NX3yPYhHW0GQR1XS
NCI-SNU-1 MoXnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTJyLkCxPVYh|ryP NHe2cmdUSU6JRWK=
GCT NHzvWZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTJyLki4NlQh|ryP MlHtV2FPT0WU
C2BBe1 NHXNfmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXu1O21sUUN3ME2yNU4yODV6IN88US=> M3uyNHNCVkeHUh?=
LB2241-RCC NXnRcppoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3PJcGlEPTB;MkGuPFQ1OSEQvF2= NWDWN|huW0GQR1XS
COLO-829 Ml;VS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTJ{LkG4O|Eh|ryP MlzvV2FPT0WU
EW-11 NUfjdHZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDNWZNpUUN3ME2yNk45ODJ{IN88US=> M1z6PXNCVkeHUh?=
NCI-H526 M1r2TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnXBTWM2OD1{Mz60O|E4KM7:TR?= NV7GO3Z6W0GQR1XS
SF295 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG[1dolKSzVyPUK0MlAzPTJizszN M4f5V3NCVkeHUh?=
D-566MG MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHf3U3dKSzVyPUK1MlI6PDNizszN M4HPPXNCVkeHUh?=
8505C NULPVFdzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm\3TWM2OD1{NT62N|MyKM7:TR?= MVHTRW5ITVJ?
HT-29 M1TDT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXqTWM2OD1{Nj6wOFMyKM7:TR?= NILRO3dUSU6JRWK=
NBsusSR MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTiTWM2OD1{Nj64NFA3KM7:TR?= M{HiTnNCVkeHUh?=
BV-173 NXnrXY9OT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnsNZdLUUN3ME2yPE4{OTh{IN88US=> M4DrXHNCVkeHUh?=
CTB-1 M2K2[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHW4UYRKSzVyPUOwMlExOzFizszN NHjMU4VUSU6JRWK=
JAR NUHHO4pVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLSVo9iUUN3ME2zNk42OzdzIN88US=> MYjTRW5ITVJ?
CAMA-1 NGrnRYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXLJR|UxRTN|LkS2NVUh|ryP M4G0dHNCVkeHUh?=
CAL-51 NGDZWYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYL3PWh5UUN3ME2zOE44OTd4IN88US=> Ml;zV2FPT0WU
A172 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV36cm43UUN3ME2zO{41QTJzIN88US=> M1[4cXNCVkeHUh?=
QIMR-WIL NYjYSZdsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTN6LkC3NFgh|ryP M3H2fXNCVkeHUh?=
AsPC-1 NHqwNZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPZWI9KSzVyPUO4MlQ3PTFizszN MkfiV2FPT0WU
MKN7 M325emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTN7LkCwO|kh|ryP MXLTRW5ITVJ?
ONS-76 NH3Te|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\sZWFMUUN3ME20N{4{ODV5IN88US=> Mne1V2FPT0WU
RS4-11 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{HYVmlEPTB;NESuNFc2OiEQvF2= Mn3oV2FPT0WU
NOS-1 MnfKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTR2Lk[wN|Eh|ryP NF\HN21USU6JRWK=
A101D NWPCcoRGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXnJR|UxRTR2LkiwNlMh|ryP M32xZnNCVkeHUh?=
HCC1806 NWLZcVhrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3PMZmlEPTB;NE[uNVE1QCEQvF2= NGjZPHpUSU6JRWK=
CAL-27 M1;2TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4HD[GlEPTB;NEeuO|I1PiEQvF2= MWrTRW5ITVJ?
BT-549 NGXQcGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3jIVmlEPTB;NEiuOVMyPSEQvF2= NYDwXZRFW0GQR1XS
LCLC-97TM1 M133TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkPMTWM2OD12OT6yOFE{KM7:TR?= MWLTRW5ITVJ?
A4-Fuk Ml3ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2rPSGlEPTB;NEmuPFQ6KM7:TR?= M4rEfXNCVkeHUh?=
OVCAR-4 MnPNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1H2TWlEPTB;NUCuNFYxOSEQvF2= NX22eYh4W0GQR1XS
HD-MY-Z MkXmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\JTWM2OD13MD63O|Y1KM7:TR?= M33ud3NCVkeHUh?=
NCI-H292 NXjhd|lGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXyVlg5UUN3ME21NE45PzV6IN88US=> MkPBV2FPT0WU
Sk-ChA-1  Mn31S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXJZ3YxNjJ34pETOVAh|ryP NF7nUHc4OiCq NX\XXphVUUN3ME23OE42PMLzMj61PO69VQ>? MV6yOVc1OjR6Mh?=
Mz-ChA-1 MmTCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWewMlI26oDVNUCg{txO MkTTO|IhcA>? NX\hUpZIUUN3ME21OE46P8LzMz60Oe69VQ>? MkLENlU4PDJ2OEK=
Smo-WT NEjOOpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETlbWdKSzVywrDv[kAyPMLibl2= MmPqNlQzQTFzMES=
Smo-D473H  NXHueYtJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxyqCxZjC3MlHDqM7:TR?= NITTSJczPDJ7MUGwOC=>
K562 MlfFSpVv[3Srb36gRZN{[Xl? NWPRbXhuOTBizszN M3zzblczKGh? NWnjbXlxemWmdXPld{B1cGViZYjwdoV{e2mxbjDv[kBIdGlzwrC= MlTMNlM{OTl6MkS=
T315I BCR-ABL BaF3 NXPTS2NmTnWwY4Tpc44hSXO|YYm= NGDUNJkyOCEQvF2= M3PsN|czKGh? MX3y[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:oIFfsbVHDqA>? M3nDOVI{OzF7OEK0
TF-1 BCR-ABL M3nKXmZ2dmO2aX;uJGF{e2G7 MmrpNVAh|ryP NGLBR4w4OiCq MUHy[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:oIFfsbVHDqA>? Mlq0NlM{OTl6MkS=

... Click to View More Cell Line Experimental Data

In vivo試験 GDC-0449 has been used to treat medulloblastoma in animal models. [2] GDC-0449 prevents the growth of primary pancreatic xenografts without non-specifically inhibiting pancreatic cell proliferation. Oral dosing of GDC-0449 causes tumor regressions in the Ptch(+/-) allograft model of medulloblastoma at doses ≥25 mg/kg and tumor growth inhibition at doses up to 92 mg/kg dosed twice daily in two ligand-dependent colorectal cancer models, D5123, and 1040830. Analysis of Hh pathway activity and PK/PD modeling reveals that GDC-0449 inhibits Gli1 with a similar IC50 in both the medulloblastoma and D5123 models (0.165 μM and 0.267 μM, respectively). Pathway modulation is linked to efficacy using an integrated PK/PD model revealing a steep relationship where > 50% of the activity of GDC-0449 is associated with >80% repression of the Hh pathway. [4]
臨床試験 GDC-0449 has entered into a phase II clinical trials in the treatment of basal cell carcinoma.
特集

プロトコル (参考用のみ)

細胞アッセイ: [2]

細胞株 MDCKII cells
濃度 20 μM
反応時間 2 hours
実験の流れ MDCKII cells are seeded into 24-well plates at a density of 3 × 105 cells per well and are allowed to attach. Medium is then changed to that containing different drugs (50 μM VP, 50 μM indomethacin, or 20 μM GDC-0449 in DMSO or DMSO alone as control, and nonfluorescent calcein-AM is added to a final concentration of 1.0 μM and incubated at 37 °C for 2 hours. Cells are then washed twice with Ca2+, Mg2+-containing Hank's balanced salt solution buffer and lysed by shaking in 0.01% Triton X-100 in PBS buffer for 1 hour at room temperature or overnight at 4 °C. The lysate is then transferred into 96-well plates, and the fluorescence signal caused by the cell-derived calcein is quantified spectrophotometrically with a SpectraMax M5 Multi-Detection Readerusing an excitation wavelength of 495 nm and an emission wavelength of 515 nm. All manipulations are performed in the dark. All readings are expressed as mean ?SEM normalized to the control.

動物実験: [4]

動物モデル Ptch(+/-) allograft model, D5123 and 1040830
製剤 In 0.5% methyl-cellulose, 0.2% tween-80
投薬量 ~ 100 mg/kg
投与方法 Orally

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Vismodegib (GDC-0449) SDF
分子量 421.3
化学式

C19H14Cl2N2O3S

CAS No. 879085-55-9
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 84 mg/mL (199.38 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose+0.2% Tween 80 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide

カスタマーフィードバック (15)


Click to enlarge
Rating
Source Gastroenterology, 2012, 143, 1319-29. Vismodegib (GDC-0449) purchased from Selleck
Method qRT-PCR/immunostaining
Cell Lines MF-HSCs
Concentrations 1 μM
Incubation Time 4 d
Results Conditional deletion of SMO in MF-HSCs recapitulated the effects of GDC-0449, causing significant down-regulation of glyco-lytic genes and MF genes.

Click to enlarge
Rating
Source Gastroenterology, 2012, 143, 1319-29. Vismodegib (GDC-0449) purchased from Selleck
Method Immunohistochemistry
Cell Lines MDR2 -/- mice
Concentrations 1 μM
Incubation Time 4 d
Results We found that treating year-old MDR2 -/- mice with a 9-day course of GDC-0449 substantially reduced the numbers of PKM2-positive cells despite the ongoing genetic stimulus for liver repair.

Click to enlarge
Rating
Source Gut, 2013, 62, 299-309. Vismodegib (GDC-0449) purchased from Selleck
Method Immunohistochemistry
Cell Lines Mdr2 -/- mice/hepatectomised mice
Concentrations
Incubation Time
Results Treatment of Mdr2 -/- mice with GDC-0449 (Hh signalling antagonist) significantly reduced the number of Gli2 and CD31 (a commonly used capillarisation marker in vivo) double-positive cells in the liver (figure A,B). Similar results were observed in partial hepatectomised mice treated with cyclopamine ( figure C).

Click to enlarge
Rating
Source Hepatology, 2011, 54, 1580-90. Vismodegib (GDC-0449) purchased from Selleck
Method qRT-PCR/Western blot
Cell Lines Huh7.5 cells
Concentrations 0-5 μM
Incubation Time 72 h
Results GDC-0449, a preclinical Hh pathway inhibitor, inhibits replication of JFH1 HCV in a dose-response manner.

Click to enlarge
Rating
Source Cancer Res, 2012, 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck
Method qRT-PCR/Western blot
Cell Lines HepG2/Huh7 cells
Concentrations 1 μmol/L
Incubation Time
Results GDC-0449 treatment of HepG2X cells decreased mRNA levels of Shh by 2.6-fold (61%, P < 0.005), PTCH1 by 6.8-fold (85%, P < 0.05), and Gli2 by 2.4-fold (58%, P < 0.05). GDC-0449 reduced Gli2 in HepG2X cells (2.2-fold; 55%, P < 0.02) and in Huh7X cells (3.8-fold; 74%, P < 0.02), but not in treated compared with untreated control cells (Fig. 1). GDC-0449 also reduced PTCH1 in HepG2X (1.8-fold; 44%, P < 0.02) and Huh7X cells (2.6-fold; 61%, P < 0.01), but not in the HBx negative cultures. Hence, HBx stimulates expression of Hhcomponents in human liver cancer cells.

Click to enlarge
Rating
Source Cancer Res, 2013, 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck
Method Phenotypic assays
Cell Lines HBx positive/negative cells
Concentrations 1 μmol/L
Incubation Time
Results GDC-0449 decreased the clonability of Huh7X cells by 2.2-fold compared with untreated cells (P < 0.01), and of HepG2X cells by 1.8-fold compared with untreated cells.

Click to enlarge
Rating
Source Cancer Res, 2014, 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck
Method Western blot/Immunohistochemistry
Cell Lines Twelve-month-old mice
Concentrations
Incubation Time
Results Untreated 12-month-old HBxTg had multiple tumors on the surface of their livers (Fig. A) although most GDC-0449-treated m ice had fewer tumors. These differences were statistically significant (Fig. B). Excised tumors showed lower levels of Gli2 in GDC- 0449-treated mice compared with controls(Fig. C).The latter was confirmed by staining , where no Gli2 was observed in treated compared with untreated mice (Fig . D).

Click to enlarge
Rating
Source Chem Biol, 2012, 19, 972-82. Vismodegib (GDC-0449) purchased from Selleck
Method Hh Activity Assays
Cell Lines ShhLightII cells/SmoM2 cells
Concentrations 0-10 μM
Incubation Time 6 h
Results Hh pathway inhibition by GDC0449, Cyc and SANT-1, as measured by both Gliluciferase induction (Figure A) and Smo ciliary localization ( Figures B and C), was dramatically reduced in vitro in the presence of FA. Thus, FA cotreatment leads to a drug-dependent alteration of cellular response to chemical inhibitors of Smo. This may occur through competition, or the requirement for a higher level of GDC-0449 to inhibit Hh-driven pathway activity in the presence of GC, but the outcome resembles the genetic resistance seen with a dominant active Smo mutation SmoM2) (Figure A).

Click to enlarge
Rating
Source Chem Biol, 2012, 19, 972-82. Vismodegib (GDC-0449) purchased from Selleck
Method Hh Activity Assays
Cell Lines Smo::EGFP/Iv s::tagRFPT cells
Concentrations 0-1000 nM
Incubation Time
Results Bud enhanced GDC0449’s activity to block Smo accumulation at the PC and Hh pathway inhibition.

Click to enlarge
Rating
Source PLoS One, 2013, 8, e74141. Vismodegib (GDC-0449) purchased from Selleck
Method H&E staining, Western blot
Cell Lines C6
Concentrations 1-20 uM
Incubation Time 24 h
Results GDC-0449 inhibited the activation of Hh signaling in the irradiated livers.

Click to enlarge
Rating
Source PLoS One, 2011, 6, e23943. Vismodegib (GDC-0449) purchased from Selleck
Method Immunohistochemistry/qRT-PCR
Cell Lines MDR2 -/- mice
Concentrations 40 mg/kg
Incubation Time 9 d
Results Overall survival between the two groups in the second cohort was equal, with no deaths in the DMSO treatment group and 1 death in the GDC-0449 treatment group secondary to iatrogenic injury. Both the liver parenchyma and tumors of treated mice showed decreased expression of the Hh pathway target Gli2 ( Figures A–B). Real-time PCR analysis of resected tumors revealed that GDC-0449 treatment released the inhibitory effects of Hh signaling on PPARa ˜ , causing a significant increase in its gene expression ( Figure C). Treatment with GDC-0449 also caused a significant decrease in expression of Gli1, another Hh target gene (Figure D ).

Click to enlarge
Rating
Source PLoS One, 2011, 6, e23943. Vismodegib (GDC-0449) purchased from Selleck
Method Immunohistochemistry
Cell Lines MDR2 -/- mice
Concentrations 40 mg/kg
Incubation Time 9 d
Results Treatment with GDC-0449 decreased α-sma-expressing myofibroblastic cells, hepatic expression of TGF- β andPDGF- β, Sirius red staining, and hydroxyproline content, demonstrating that Hh pathway inhibition reduced liver fibrosis.

Click to enlarge
Rating
Source PLoS One, 2011, 6, e23943. Vismodegib (GDC-0449) purchased from Selleck
Method Immunohistochemistry/QRT-PCR analysis
Cell Lines MDR2 -/- mice
Concentrations 40 mg/kg
Incubation Time 9 d
Results Immunohistochemistry and quantitative morphometry demonstrated that inhibition of the Hh pathway with GDC-0449 significantly decreased osteopontin staining within primary liver tumors ( Figure A ). Similar treatment-related decreases in CD44 + tumor cells were also noted (Figure B). Gene expression analysis showed that expression of both osteopontin and CD44 mRNAs also tended to decrease in GDC-0449-treated mice ( Figure C ).

Click to enlarge
Rating
Source J Neuroncol , 2011, 105, 475-483. Vismodegib (GDC-0449) purchased from Selleck
Method Quantitative RT-PCR
Cell Lines Mouse medulloblastoma primary cells (U51669)
Concentrations 0-100 nM
Incubation Time
Results GDC-0449 effectively suppressed Gli1, which is a Shh pathway target gene.

Click to enlarge
Rating
Source Vismodegib (GDC-0449) purchased from Selleck
Method Flow cytometry
Cell Lines ABCG2-expressing cell sublines
Concentrations 50 µM
Incubation Time
Results We examined the inhibition of Pp-18 efflux to assess reported inhibitors of ABCG2-mediated drug resistance. The fold value is defined as the accumulation of Pp-18 in the presence of an inhibitor divided by the accumulation of Pp-18 in the absence of an inhibitor. vismodegib demonstrated a significant increase in Pp-18 accumulation in both human and mouse ABCG2-expressing cell lines.

文献中の引用 (33)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related ヘッジホッグ/スムーズンド 阻害剤

  • Smoothened Agonist (SAG) HCl

    Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist.

  • SB225002

    SB225002 is a potent, and selective CXCR2 antagonist with IC50 of 22 nM for inhibiting interleukin IL-8 binding to CXCR2, > 150-fold selectivity over the other 7-TMRs tested.

  • SB-334867

    SB-334867 is a selective orexin-1 (OX1) receptor antagonist.

  • BAF312 (Siponimod)

    BAF312 (Siponimod) is a next-generation S1P receptor modulator, selective for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, respectively.

  • Cyclopamine

    Cyclopamineは、スムーズにされる(SMO)ものの経路敵対者に合図している特定のハリネズミ(Hh)で、 IC50 が 46 nM。

  • GANT61

    GANT61 is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation.

  • Purmorphamine

    Purmorphamine, which directly binds and activates Smoothened, blocks BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM and also is an inducer of osteoblast differentiation with EC50 of 1 μM.

  • LDE225 (NVP-LDE225,Erismodegib)

    LDE225 (NVP-LDE225,Erismodegib)は、スムーズにされた 敵対者で、IC50 がそれぞれ 1.3 nM (mouse)と 2.5 nM (human)です。

  • Taladegib (LY2940680)

    Taladegib (LY2940680)はSmoレセプターと結合して、強力にHhシグナリングを妨げます。

最近チェックしたアイテム

Tags: Vismodegib (GDC-0449)を買う | Vismodegib (GDC-0449)供給者 | Vismodegib (GDC-0449)を購入する | Vismodegib (GDC-0449)費用 | Vismodegib (GDC-0449)生産者 | オーダーVismodegib (GDC-0449) | Vismodegib (GDC-0449)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ