Vismodegib (GDC-0449)

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。

価格 在庫  
USD 113 あり
USD 181 あり
USD 214 あり
USD 466 あり
USD 1222 あり
電話番号: + 81 3-5632-9610mail@cosmobio.co.jp

Vismodegib (GDC-0449) 化学構造
分子量: 421.3

高品質保証

文献中の引用(34)

カスタマーフィードバック(16)

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 NVfC[I9KT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWPJR|UxRTBwMEeyOFgh|ryP MmjxV2FPT0WU
HCE-T M{myT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX\JR|UxRTFwM{KyOFch|ryP MWLTRW5ITVJ?
D-542MG MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTFwOE[3N|ch|ryP MnGwV2FPT0WU
23132-87 MkLhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnPTWM2OD12LkSwNVQ4KM7:TR?= NHOwflFUSU6JRWK=
HDLM-2 NWXwZo9QT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\MTWM2OD16LkC0O|Y3KM7:TR?= NEHONYZUSU6JRWK=
ACN M3vab2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnO5TWM2OD16LkWwNVA6KM7:TR?= MW\TRW5ITVJ?
HuO-3N1 MmDhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTlwNkCxNFgh|ryP M1\we3NCVkeHUh?=
BHT-101 MoHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TFdmlEPTB;MUGuN|gh|ryP MorFV2FPT0WU
KYSE-150 MkC5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPBTWM2OD1zMT61PFQyKM7:TR?= NF7HZ4tUSU6JRWK=
MC-IXC NGjlRXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzLZ2ZKSzVyPUGyMlIzQTJizszN NYnaN4c4W0GQR1XS
D-423MG NIfPO|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1rKZWlEPTB;MUKuO|Y2PyEQvF2= NXzX[Yx1W0GQR1XS
NY NFvxe5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHL0TZVKSzVyPUG0Mlg6ODNizszN NXjLOmh4W0GQR1XS
HOS MnTxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7wdFdmUUN3ME2xOU43PzF7IN88US=> MVrTRW5ITVJ?
NB7 NHOzSnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnTTWM2OD1zNT64PVEh|ryP NEPUNJJUSU6JRWK=
DMS-273 NHzvS2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3[0fmlEPTB;MU[uOlcyOyEQvF2= M3TFNnNCVkeHUh?=
MDA-MB-361 MnK1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlj6TWM2OD1zNz6yO|EyKM7:TR?= M2nWTnNCVkeHUh?=
DU-145 NUT2fY5kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmWyTWM2OD1zOD6zNkDPxE1? M{LuWHNCVkeHUh?=
NCI-H82 Mn;NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTF7LkizPFYh|ryP MX\TRW5ITVJ?
NCI-SNU-1 MlPaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnHDTWM2OD1{MD6wNVk3KM7:TR?= MV\TRW5ITVJ?
GCT NFi3cFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmDvTWM2OD1{MD64PFI1KM7:TR?= NXjJdFZVW0GQR1XS
C2BBe1 M3HNS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTBTWM2OD1{MT6xNFU5KM7:TR?= Ml7tV2FPT0WU
LB2241-RCC Mnv1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MknQTWM2OD1{MT64OFQyKM7:TR?= MlLMV2FPT0WU
COLO-829 M{fCPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXLSpRKSzVyPUKyMlE5PzFizszN MnK4V2FPT0WU
EW-11 MonlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M33aW2lEPTB;MkKuPFAzOiEQvF2= M2TSdHNCVkeHUh?=
NCI-H526 NVWzbnVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUHnWpBpUUN3ME2yN{41PzF5IN88US=> MljoV2FPT0WU
SF295 NWSzUJB7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV73b2I5UUN3ME2yOE4xOjV{IN88US=> M3;oZXNCVkeHUh?=
D-566MG M{eweWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDhTGhMUUN3ME2yOU4zQTR|IN88US=> M3nWbnNCVkeHUh?=
8505C NXK5c3ViT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1P2OWlEPTB;MkWuOlM{OSEQvF2= MYXTRW5ITVJ?
HT-29 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrGZmxMUUN3ME2yOk4xPDNzIN88US=> NFnvOWRUSU6JRWK=
NBsusSR M4fV[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoL3TWM2OD1{Nj64NFA3KM7:TR?= MnjuV2FPT0WU
BV-173 MnKyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PPZWlEPTB;MkiuN|E5OiEQvF2= MXPTRW5ITVJ?
CTB-1 NYjifpRqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{W0NmlEPTB;M{CuNVA{OSEQvF2= MXvTRW5ITVJ?
JAR MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEi1WmFKSzVyPUOyMlU{PzFizszN M3K5eXNCVkeHUh?=
CAMA-1 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2PnbWlEPTB;M{OuOFYyPSEQvF2= NW[3SHdIW0GQR1XS
CAL-51 M1XJRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTN2LkexO|Yh|ryP Mlj0V2FPT0WU
A172 NEXIOY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDXbFNrUUN3ME2zO{41QTJzIN88US=> M4DGdXNCVkeHUh?=
QIMR-WIL NGXFPYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFu2OVdKSzVyPUO4MlA4ODhizszN MYfTRW5ITVJ?
AsPC-1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\PNXo1UUN3ME2zPE41PjVzIN88US=> MoDYV2FPT0WU
MKN7 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG\p[4hKSzVyPUO5MlAxPzlizszN MkPVV2FPT0WU
ONS-76 NWLHdXBuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVq0VVlvUUN3ME20N{4{ODV5IN88US=> MUfTRW5ITVJ?
RS4-11 NHPCT3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH2wUYFKSzVyPUS0MlA4PTJizszN M2m4XHNCVkeHUh?=
NOS-1 NUHmfm1OT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUCxU5FXUUN3ME20OE43ODNzIN88US=> NHzTN2lUSU6JRWK=
A101D M1TqeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUTJR|UxRTR2LkiwNlMh|ryP M1XCRnNCVkeHUh?=
HCC1806 MkHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1flUmlEPTB;NE[uNVE1QCEQvF2= Mk\zV2FPT0WU
CAL-27 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTR5LkeyOFYh|ryP MVXTRW5ITVJ?
BT-549 NFyyclNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTR6LkWzNVUh|ryP NGS0VpJUSU6JRWK=
LCLC-97TM1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPRfHVHUUN3ME20PU4zPDF|IN88US=> NUDIVmd{W0GQR1XS
A4-Fuk NVTXemJiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M33mUmlEPTB;NEmuPFQ6KM7:TR?= MnziV2FPT0WU
OVCAR-4 M{fiXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;CTXBKSzVyPUWwMlA3ODFizszN M2jVWnNCVkeHUh?=
HD-MY-Z Mof4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEj0Wm1KSzVyPUWwMlc4PjRizszN MXLTRW5ITVJ?
NCI-H292 M2\H[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHT2VodKSzVyPUWwMlg4PThizszN NE\wSW5USU6JRWK=
Sk-ChA-1  MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;2T|AvOjYkgKO1NEDPxE1? M17jXFczKGh? MULJR|UxRTd2LkW0xtEzNjV6zszN M3jYZVI2PzR{NEiy
Mz-ChA-1 M3r3fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWSwMlI26oDVNUCg{txO MkfDO|IhcA>? M{\1T2lEPTB;NUSuPVfDuTNwNEZOwG0> M4ryT|I2PzR{NEiy
Smo-WT NGHpV|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfhb5puUUN3MNMgc4YhOTUEoH7N NWPReolLOjR{OUGxNFQ>
Smo-D473H  NEHaR4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDifZJKSzVywrDv[kA4NjIEoN88US=> NHezeo4zPDJ7MUGwOC=>
K562 M3PwZmZ2dmO2aX;uJGF{e2G7 M3XvSVExKM7:TR?= NWn3fG1CPzJiaB?= MVny[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:oIFfsbVHDqA>? MkfwNlM{OTl6MkS=
T315I BCR-ABL BaF3 M2jKVWZ2dmO2aX;uJGF{e2G7 NV;GVmZROTBizszN NELhTog4OiCq M1nnU5Jm\HWlZYOgeIhmKGW6cILld5Nqd25ib3[gS4xqOcLi MUmyN|MyQTh{NB?=
TF-1 BCR-ABL Mmi2SpVv[3Srb36gRZN{[Xl? MmnzNVAh|ryP MYO3NkBp NWjKbFRvemWmdXPld{B1cGViZYjwdoV{e2mxbjDv[kBIdGlzwrC= MVKyN|MyQTh{NB?=

... 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 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 84 mg/mL (199.38 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
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 (34)

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は1種の細胞浸透性Smoothened (Smo)の作動剤で、Shh-LIGHT2細胞の中でEC50 値は3 nMです。

  • 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