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 MoS5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXOTVhOUUN3ME2wMlA4OjR6IN88US=> NWi2UW9[W0GQR1XS
HCE-T NXLHZot1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlfGTWM2OD1zLkOyNlQ4KM7:TR?= MofMV2FPT0WU
D-542MG NEXqVYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13pXGlEPTB;MT64Olc{PyEQvF2= NUXUV|JUW0GQR1XS
23132-87 NH;SOotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DzdmlEPTB;ND60NFE1PyEQvF2= MmHTV2FPT0WU
HDLM-2 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGq2doJKSzVyPUiuNFQ4PjZizszN M3PWOHNCVkeHUh?=
ACN MkftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\kWYhJUUN3ME24MlUxOTB7IN88US=> NHPIfIlUSU6JRWK=
HuO-3N1 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHNTWM2OD17Lk[wNVA5KM7:TR?= NHjvPJZUSU6JRWK=
BHT-101 NWrnbJU{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTFzLkO4JO69VQ>? NYf4WnNEW0GQR1XS
KYSE-150 NXTJfppjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrrO3VKSzVyPUGxMlU5PDFizszN MXnTRW5ITVJ?
MC-IXC MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTF{LkKyPVIh|ryP MkXKV2FPT0WU
D-423MG NFjSW|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV63[5hpUUN3ME2xNk44PjV5IN88US=> MnfsV2FPT0WU
NY MojxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEXidWlKSzVyPUG0Mlg6ODNizszN MnLlV2FPT0WU
HOS NFy4eG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILJUVdKSzVyPUG1MlY4OTlizszN NUnFWWdNW0GQR1XS
NB7 Ml7mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPHfINKSzVyPUG1Mlg6OSEQvF2= M2f0dXNCVkeHUh?=
DMS-273 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYLp[5M2UUN3ME2xOk43PzF|IN88US=> NHXHTndUSU6JRWK=
MDA-MB-361 NFLseWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnryTWM2OD1zNz6yO|EyKM7:TR?= M1z6[HNCVkeHUh?=
DU-145 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTmeFhmUUN3ME2xPE4{OiEQvF2= MY\TRW5ITVJ?
NCI-H82 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\FbYxOUUN3ME2xPU45Ozh4IN88US=> Mor4V2FPT0WU
NCI-SNU-1 NULDTnVGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFH3eGtKSzVyPUKwMlAyQTZizszN MXLTRW5ITVJ?
GCT M2qxNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTJyLki4NlQh|ryP NUjNNIk3W0GQR1XS
C2BBe1 M4TLNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3XYcWlEPTB;MkGuNVA2QCEQvF2= MVLTRW5ITVJ?
LB2241-RCC MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTJzLki0OFEh|ryP NF7qcIxUSU6JRWK=
COLO-829 M3XHfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zYWGlEPTB;MkKuNVg4OSEQvF2= MkLRV2FPT0WU
EW-11 MoPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\DeWlEPTB;MkKuPFAzOiEQvF2= Ml\UV2FPT0WU
NCI-H526 M4H1fWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYTSNVVqUUN3ME2yN{41PzF5IN88US=> NYrmWFY6W0GQR1XS
SF295 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTJ2LkCyOVIh|ryP NETrT21USU6JRWK=
D-566MG NXXZWYpnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRTJ3LkK5OFMh|ryP M1XzW3NCVkeHUh?=
8505C NULnV3N1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTJ3Lk[zN|Eh|ryP NUnjXVlwW0GQR1XS
HT-29 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13neGlEPTB;Mk[uNFQ{OSEQvF2= MnTYV2FPT0WU
NBsusSR MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfFVWdKSzVyPUK2MlgxODZizszN M1rPfHNCVkeHUh?=
BV-173 Mlr6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NILvVVhKSzVyPUK4MlMyQDJizszN NGe4SZlUSU6JRWK=
CTB-1 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnz3TWM2OD1|MD6xNFMyKM7:TR?= MoLFV2FPT0WU
JAR M{iyWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3hemxKSzVyPUOyMlU{PzFizszN M1OxNXNCVkeHUh?=
CAMA-1 MlX6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjWV5FKSzVyPUOzMlQ3OTVizszN M3zycXNCVkeHUh?=
CAL-51 NE\1VolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTGeZpSUUN3ME2zOE44OTd4IN88US=> MlfsV2FPT0WU
A172 NIfjN5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\afWNKSzVyPUO3MlQ6OjFizszN M1zHVnNCVkeHUh?=
QIMR-WIL MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4rwemlEPTB;M{iuNFcxQCEQvF2= MmPpV2FPT0WU
AsPC-1 M1;wNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVLJR|UxRTN6LkS2OVEh|ryP NF25PVNUSU6JRWK=
MKN7 M3PH[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrXT4pNUUN3ME2zPU4xODd7IN88US=> MWfTRW5ITVJ?
ONS-76 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELmU4NKSzVyPUSzMlMxPTdizszN M1nDXXNCVkeHUh?=
RS4-11 NVvYdmRHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\KTWZwUUN3ME20OE4xPzV{IN88US=> MYDTRW5ITVJ?
NOS-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\WTWM2OD12ND62NFMyKM7:TR?= MXTTRW5ITVJ?
A101D MljoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlHhTWM2OD12ND64NFI{KM7:TR?= MUHTRW5ITVJ?
HCC1806 NIfKOGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWCy[mwyUUN3ME20Ok4yOTR6IN88US=> NWDQOo1EW0GQR1XS
CAL-27 M2\qV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFraVopKSzVyPUS3MlczPDZizszN MmHaV2FPT0WU
BT-549 M{DnXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;xU4Z4UUN3ME20PE42OzF3IN88US=> NWjlUppmW0GQR1XS
LCLC-97TM1 M2q0ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlflTWM2OD12OT6yOFE{KM7:TR?= M4D2UnNCVkeHUh?=
A4-Fuk NWGwUm1ST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PNNmlEPTB;NEmuPFQ6KM7:TR?= MWLTRW5ITVJ?
OVCAR-4 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPaTWM2OD13MD6wOlAyKM7:TR?= NH;MO4JUSU6JRWK=
HD-MY-Z NWHRd4JsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGHtWoNKSzVyPUWwMlc4PjRizszN NELEdI9USU6JRWK=
NCI-H292 MnXiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoGxTWM2OD13MD64O|U5KM7:TR?= MlPJV2FPT0WU
Sk-ChA-1  M2fENmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXuwMlI26oDVNUCg{txO NV7SdoxtPzJiaB?= MojYTWM2OD15ND61OOKyOi53ON88US=> M{HYdVI2PzR{NEiy
Mz-ChA-1 NETZUoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUn2XppIOC5{NfMAl|UxKM7:TR?= MlTXO|IhcA>? MoLGTWM2OD13ND65O:KyOy52Nd88US=> NV;6S3VUOjV5NEK0PFI>
Smo-WT MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;PUnlKSzVywrDv[kAyPMLibl2= MVmyOFI6OTFyNB?=
Smo-D473H  M{G2emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEe0eW5KSzVywrDv[kA4NjIEoN88US=> NU\IOWhDOjR{OUGxNFQ>
K562 NHmyOHJHfW6ldHnvckBCe3OjeR?= Mni1NVAh|ryP NGjNcWU4OiCq NIfOOolz\WS3Y3XzJJRp\SCneIDy[ZN{cW:wIH;mJGdtcTIEoB?= NVH1eFlUOjN|MUm4NlQ>
T315I BCR-ABL BaF3 M4TRT2Z2dmO2aX;uJGF{e2G7 MWmxNEDPxE1? MmPUO|IhcA>? MVPy[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:oIFfsbVHDqA>? MoDWNlM{OTl6MkS=
TF-1 BCR-ABL NGC2cYFHfW6ldHnvckBCe3OjeR?= M1PMTVExKM7:TR?= MlTsO|IhcA>? M2fEd5Jm\HWlZYOgeIhmKGW6cILld5Nqd25ib3[gS4xqOcLi MnLvNlM{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 2% DMSO+30% PEG 300+5% Tween 80+ddH2O 10mg/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

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