Vismodegib (GDC-0449)

製品コードS1082

Vismodegib (GDC-0449)化学構造

分子量(MW):421.3

Vismodegib (GDC-0449)は一種の有効で、新たで、特異性的なhedgehog阻害剤ですが、無細胞試験でIC50値が3nMになって、P-gpも抑制して、このIC50値が3.0μMになります。

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文献中の使用例(34)

カスタマーフィードバック(16)

  • SMOΔC captured on cholesterol beads in the presence of increasing concentrations of free vismodegib or 20(S)-OHC (h). Results from one of two independent pull-down experiments are shown.

    Nature, 2016, 535(7613):517-22.. Vismodegib (GDC-0449) purchased from Selleck.

    (B) qRT-PCR analysis and immunostaining of murine HSCs treated with GDC-0449 on culture days 4 through 7 (to inhibit SMO) or culture day 7 SMO-LoxP HSCs treated with adenoviral Cre on day 4 (to disrupt the Smo gene).

    Gastroenterology 2012 143, 1319-29. Vismodegib (GDC-0449) purchased from Selleck.

  • Hh signaling controls metabolic reprogramming during liver injury in vivo. Immunohistochemistry identifies cells expressing the M2 isozyme of PKM2, a specific marker of glycolytic activity, ( C) inhibited in aged MDR2 -/- mice by GDC-0449.

    Gastroenterology 2012 143, 1319-29. Vismodegib (GDC-0449) purchased from Selleck.

    Inhibition of Hedgehog (Hh) pathway prevents liver sinusoidal endothelial cell (LSEC) capillarisation in vivo. (A) Liver sections from dimethyl sulphoxide (DMSO) and GDC-0449-treated Mdr2 -/- mice were double-stained for Gli2 (brown, Hh target gene) and CD31 (blue, capillarisation marker). Note that LSEC co-express Gli2 and CD31 (arrow). Scale bar: 10 μm. The number of Gli2/CD31 double-positive cells per field (B) was counted in five random fields per mouse, ***p < 0.001, n = 3. (C) Liver sections from vehicle and cyclopamine-treated partial hepatectomised (PHx) mice were stained for Gli2 and CD31, and the number of Gli2/CD31 double-positive cells was counted. **p< 0.01, n = 3. Cyc, cyclopamine

    Gut 2013 62, 299-309. Vismodegib (GDC-0449) purchased from Selleck.

  • GDC-0449, a preclinical Hh pathway inhibitor, inhibits replication of JFH1 HCV in a dose-response manner. (A) Huh7.5 cells were mock-infected (control), infected with JFH1 HCV alone, JFH1 HCV plus vehicle (JFHþ DMSO), and JFH1 HCV plus GDC-0449 5 μM concentration. After 72 hours, relative RNA expression was analyzed for HCV RNA, Shh, and Gli1. Results are expressed as relative fold expression with mock-infected expression indexed to 1, except for HCV RNA sample, in which case JFH1 HCV alone was indexed to 1. (B) Protein lysates were created from the above-described experiment. Antibodies to HCV Core, Shh, and a-tubulin were used for analysis. (C) The above experiment was repli-cated with var ying concentrations of GDC-0449 to assess dose-response of anti-HCV activity. Concentrations used were: 0 μM, 0.05 μM, 0.5 μM, 5 μM, and 25 μM. After 72 hours, relative RNA expression was analyzed for HCV RNA, Shh, and Gli1. Results are expressed as relative fold expression with mock-infected expression indexed to 1, except for HCV RNA sample, in which case JFH1 HCV alone was indexed to 1. *P < 0.05, **P < 0.01, † P < 0.005.

    Hepatology 2011 54, 1580-90. Vismodegib (GDC-0449) purchased from Selleck.

    Changes in markers of Hh signaling were determined in HBx positive (X) and negative (CAT) HepG2 and Huh7 cells treated with DMSO or GDC- 0449. A and B, qRT- PCR results are shown as the mean±SEM of triplicate experiments. P < 0.05; P < 0.01;†, P < 0.005. C, representative Western blot analysis of total extracts from the cells above. D, quantification o f protein levels (mean expression±SD of 3 assays for each marker). DMSO controls are the black bars and cells treated with 1 μmol/L GDC- 0449 are the white bars.

    Cancer Res 2012 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck.

  • Phenotypic changes associated with Hh signaling in HBx positive and negative cells with or without GDC-0449. A, rep resentative images of HBx expressing cells that migrated through Matrigel basement membrane (×200). B, quantifi cation of the results in A (mean expression±D of 3 assays ). Cells were treated with DMSO (dark bars) or with GDC-0449 (light bars). P < 0.01; P < 0.02. C, anchorage-independent growth of Huh7X and HepG2X with or without GDC-0449. D, quantification o f the results in C (mean expression±D of 3 assays). Cells were treated with DMSO (dark bars) or with GDC-0449 (light bars).

    Cancer Res 2013 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck.

    Relationship between Hh signaling and HCC in HBxTg. A, HCC nodules (circled) on the surface of the liver. B, the number of visible nodules observed on livers ( n = 6 HBxTg per group) after inject ions of vehicle (dark bars) or GDC- 0449 (light bars). Tumor numbers for individual mice are shown above each bar. The average tumor number is shown above each group. C, Western blot analysis for Gli2 in livers from transgenic mice treated with vehicle (-) or GDC- 0449 (+). D, staining for Gli2 and Shh on serial section s of tumors (T) and nontumor (NT) livers from HBxTg treated with vehicle (top) or GDC- 0449 (bottom). Magnification is ?00 for each panel and ?00 for each insert.

    Cancer Res 2014 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck.

  • (A) GDC0449 dose-dependent inhibition of Shh-stimulated Hh pathway activity in the presence or absence of 10 μM FA , or SmoM2 expressing cell lines. (B) Representative images of Smo::EGFP/Ivs: :tagRFPT cells treated with GDC0449 and Shh in the presence or absence of 10 μM FA. GDC0449 was coapplied at 111 and 1,111 nM respectively with Shh and Shh+FA . (C) Relative Smo::EGFP+ cilium count of GDC0 449’s dose-dependent inhibition of Shh ligand-stimulated accumulation of cilia ry Smo in the presence or absence of 10 μM FA. Measurements were performed in quadruplicate. Several hundred cells were analyzed in each sample to asses s the accumulation of Smo in the PC from data in (B). Data plotte d are mean (±SD). Scale bar: 5 μm.

    Chem Biol 2012 19, 972-82. Vismodegib (GDC-0449) purchased from Selleck.

    Quantification of Smo ciliary localization (A) and representative images (B) of Smo::EGFP/Iv s::tagRFPT cells treated with GDC0449 and Shh in the presence or absence of 10 μM Bud. In (B), GDC0449 was coapplied at 1.6 nM with Shh and Shh+Bud, respectively. (C) GDC0449 dose-dependent inhibition of Shh-stimulated Hh pathway activity in the presence or absen ce of 10 μM Bud. Data plotted are mean (± SD) from four biological replicates (A) analyzing over a thousand of cells or three biological replicates (C). Scale bar: 5 μm.

    Chem Biol 2012 19, 972-82. Vismodegib (GDC-0449) purchased from Selleck.

  • Hh inhibitor, GDC-0449, blocks hepatic Hh activity in the irradiated mice. (A) H&E staining shows less fat accumulation in hepatocytes in liver from representative irradiated mice with GDC-0449 (IR+GDC) (X40). (B) Relative liver weight/body weight of mice. (C) The values of AST and ALT are graphed. (D) QRT-PCR analysis of liver mRNA from DMSO (DMSO), radiation treated mice with (IR+GDC) or without GDC-0449 (IR+DMSO) for smo, and gli2 ((n≥4 mice/group). Mean±SD results are graphed. (E) and (F). Western blot analysis of Smo, and Gli2 (GAPDH was used as an internal control). Data shown represent one of three experiments with similar results (E: Immuoblot/F: Band density) (n≥4 mice/group). Data represent the mean±SD of three independent experiments (*p<0.05, **p<0.005).

    PLoS One 2013 8, e74141. Vismodegib (GDC-0449) purchased from Selleck.

    Hedgehog (Hh) inhibitor, GDC-0449, abrogates effects of Hh signaling within liver parenchyma and HCC nodules. A. Liver sections stained for Gli2 from representative DMSO- and GDC-0449- treated mice (40×). Quantitative Gli2 immunohistochemistry data in non-tumor livers of mice treated with DMSO or GDC-0449 (n = 9–10/group) are graphed as mean ±SEM (**p < 0.01 . The number of ductular cells with Gli2 positive staining were counted in each portal tract/section under 40×magnification. B. Tumor sections from the same mice were also stained to demonstrate Gli2. Results from representative DMSO- and GDC-0449-treated mice are displayed. Quantitative Gli2 immunohistochemistry data were generated by counting nuclear Gli2 positive ductular and hepatocytic cells in tumor sections under 40×magnification. Results are graphed as mean ± SEM Gli2-positive cells/40×high power field (**p < 0.01)C–D Quantitative reverse transcription-PCR (qRT-PCR) analysis of whole liver RNA from DMSO-(open bar) and GDC-0449 (black bar) treated mice. C. PPAR-c, a gene that is normally repressed by Hh signaling. D.Gli1, a gene that is induced by Hh signaling. Mean±SEM are graphed (**p < 0.01).

    PLoS One 2011 6, e23943. Vismodegib (GDC-0449) purchased from Selleck.

  • GDC-0449 treatment reduces fibrosis in Mdr2 -/- mice. A. Immunohistochemical staining for α-SMA (top panel) and Sirius red (bottom panel) in sections of non-tumor liver from representative age-matched Mdr2 -/- and wildtype mice (10×). B. Pooled Hepatic hydroxyproline content of 2-52 wk-old wildtype (WT) and age-matched Mdr2 -/- mice (n = 3–5/group). Results in Mdr2 -/- mice were normalized to that of age-matched WT mice and graphed as fold change. Data are displayed as mean +/- SD (*p < 0.05)C. Non-tumor liver sections stained fora-SMA (top panel, 20×) and Sirius red (bottom panel, 10×) in representative DMSO- and GDC- treated Mdr2 -/- mice. D.Heptic hydroxyproline content of DMSO- and GDC- treated mice (n = 9/group). Results in GDC-0449-treated mice were normalized to that of DMSO vehicle-treated mice and graphed as fold change. Data are displayed as Mean +/- SEM (*p < 0.05).

    PLoS One 2011 6, e23943. Vismodegib (GDC-0449) purchased from Selleck.

    Inhibition of Hh signaling decreases osteopontin and osteopontin-responsive (CD44) positive cells in tumors and peritumoral tissues of aged Mdr2 -/- mice. A. Tumor sections from representative DMSO- and GDC-0449 treated Mdr2 -/- mice were stained to demonstrate osteopontin (OPN) Representative sections are displayed ( Right panel ). OPN staining was quantified by morphometric analysis of at least 5 HPF per tumor section using 20譵agnification (n = 5 mice/group). Results in the GDC-0449-treated group were normalized to that of the group treated with DMSO vehicle and graphed as fold change. Data are displayed as Mean 盨EM (**p < 0.01). B. Immunohistochemical staining for the osteopontin receptor, CD44, in peri-tumoral tissues of representative DMSO- and GDC-0449- treated Mdr2 -/- mice. (Right panel ) CD44 staining was quantified by morphometric analysis as described in A. Results in GDC-0449-treated mice were normalized to those of vehicle-treated controls and graphed as Mean盨EM (**p < 0.01). C. QRT-PCR analysis of liver tumor RNA from DMSO- (open bar) and GDC-0449- (closed bar) treated Mdr2 -/- mice for OPN (left) and CD44 (right). After normalization to results in the DMSO-treated group, Mean盨EM were graphed (*p < 0.05).

    PLoS One 2011 6, e23943. Vismodegib (GDC-0449) purchased from Selleck.

  • Mouse medulloblastoma primary cells (U51669) showed inhibition of Gli1 by GDC-0499 in dose dependent manner. *P<0.01.

     

     

    J Neuroncol 2011 105, 475-483. Vismodegib (GDC-0449) purchased from Selleck.

     

    Flow cytometry of purpurin-18 accumulation in the presence of the following inhibitors in mouse and human ABCG2-expressing sublines demonstrated a similar pattern of inhibition. 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 absense of any inhibitor. Data represent mean±S.D. of three observation.

    Vismodegib (GDC-0449) purchased from Selleck.

製品安全説明書

Hedgehog/Smoothened阻害剤の選択性比較

生物活性

製品説明 Vismodegib (GDC-0449)は一種の有効で、新たで、特異性的なhedgehog阻害剤ですが、無細胞試験でIC50値が3nMになって、P-gpも抑制して、このIC50値が3.0μMになります。
ターゲット
Hedgehog [1]
(Cell-free assay)
3 nM
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
IGROV-1 M2OyfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M37NfWlEPTB;MD6wO|I1QCEQvF2= M3\N[3NCVkeHUh?=
HCE-T MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jRVGlEPTB;MT6zNlI1PyEQvF2= MXHTRW5ITVJ?
D-542MG NILveVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTFwOE[3N|ch|ryP NGG5OItUSU6JRWK=
23132-87 NXrKNJQ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nDRmlEPTB;ND60NFE1PyEQvF2= NVL5[ph6W0GQR1XS
HDLM-2 M2LKcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTzTWM2OD16LkC0O|Y3KM7:TR?= MYrTRW5ITVJ?
ACN Ml:1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRThwNUCxNFkh|ryP M2HXbHNCVkeHUh?=
HuO-3N1 MonqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTlwNkCxNFgh|ryP NXPpXZdrW0GQR1XS
BHT-101 MkmxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTFzLkO4JO69VQ>? NGXiVJNUSU6JRWK=
KYSE-150 M4P1Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TaPWlEPTB;MUGuOVg1OSEQvF2= M4LSSHNCVkeHUh?=
MC-IXC MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmnrTWM2OD1zMj6yNlkzKM7:TR?= MWHTRW5ITVJ?
D-423MG MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLxTWM2OD1zMj63OlU4KM7:TR?= MoHkV2FPT0WU
NY MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH[5TJhKSzVyPUG0Mlg6ODNizszN MXvTRW5ITVJ?
HOS Mm\tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fEU2lEPTB;MUWuOlcyQSEQvF2= NI\EdYhUSU6JRWK=
NB7 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTQVpllUUN3ME2xOU45QTFizszN M3TjO3NCVkeHUh?=
DMS-273 M{mzTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrmSVJPUUN3ME2xOk43PzF|IN88US=> MVrTRW5ITVJ?
MDA-MB-361 NHvsSIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYi2UJNbUUN3ME2xO{4zPzFzIN88US=> MlPiV2FPT0WU
DU-145 M{PrWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTF6LkOyJO69VQ>? MWTTRW5ITVJ?
NCI-H82 NHzZXJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHycYZKSzVyPUG5Mlg{QDZizszN NXzjdXJVW0GQR1XS
NCI-SNU-1 NXj2SlI6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTJyLkCxPVYh|ryP M{S4fHNCVkeHUh?=
GCT NX7qW5ZvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{X2bmlEPTB;MkCuPFgzPCEQvF2= NIXadWNUSU6JRWK=
C2BBe1 M1jEbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrCNlBKSzVyPUKxMlExPThizszN NUTSXIIzW0GQR1XS
LB2241-RCC NVzkcGxrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoDtTWM2OD1{MT64OFQyKM7:TR?= NFOxd5pUSU6JRWK=
COLO-829 NEHpblRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnnRTWM2OD1{Mj6xPFcyKM7:TR?= MVjTRW5ITVJ?
EW-11 MnfhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkDITWM2OD1{Mj64NFIzKM7:TR?= NI\nN2hUSU6JRWK=
NCI-H526 NXL1R2h5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\QTWM2OD1{Mz60O|E4KM7:TR?= NWPB[nFrW0GQR1XS
SF295 MkfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTJ2LkCyOVIh|ryP NGDnNo1USU6JRWK=
D-566MG NIGxTJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;1eWpHUUN3ME2yOU4zQTR|IN88US=> Ml3xV2FPT0WU
8505C MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmTDTWM2OD1{NT62N|MyKM7:TR?= NX3oPYxDW0GQR1XS
HT-29 MmnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTJ4LkC0N|Eh|ryP NVWxNIdIW0GQR1XS
NBsusSR NVm4XnNTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nYe2lEPTB;Mk[uPFAxPiEQvF2= M1v6UXNCVkeHUh?=
BV-173 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mom0TWM2OD1{OD6zNVgzKM7:TR?= M1WwXXNCVkeHUh?=
CTB-1 NUTLWYtZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVHJR|UxRTNyLkGwN|Eh|ryP MlX2V2FPT0WU
JAR NIny[Y9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\FRZFpUUN3ME2zNk42OzdzIN88US=> MnS4V2FPT0WU
CAMA-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU\JR|UxRTN|LkS2NVUh|ryP M3OweHNCVkeHUh?=
CAL-51 NH;QOpRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnQSlRKSzVyPUO0MlcyPzZizszN MlHEV2FPT0WU
A172 M4DucGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXrJR|UxRTN5LkS5NlEh|ryP MmLTV2FPT0WU
QIMR-WIL M3y2[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTN6LkC3NFgh|ryP NV7GdpQxW0GQR1XS
AsPC-1 Mn3oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmn4TWM2OD1|OD60OlUyKM7:TR?= MlLlV2FPT0WU
MKN7 NHjLXINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlThTWM2OD1|OT6wNFc6KM7:TR?= MWnTRW5ITVJ?
ONS-76 M3XDNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjUdZlEUUN3ME20N{4{ODV5IN88US=> MYjTRW5ITVJ?
RS4-11 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTq[pJKSzVyPUS0MlA4PTJizszN MVnTRW5ITVJ?
NOS-1 NUfldYFiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYDJR|UxRTR2Lk[wN|Eh|ryP Mmq1V2FPT0WU
A101D M3v2NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTYWGl6UUN3ME20OE45ODJ|IN88US=> M4PLdnNCVkeHUh?=
HCC1806 M3;DVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrDbYxnUUN3ME20Ok4yOTR6IN88US=> NFHNNHNUSU6JRWK=
CAL-27 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHLmSoFKSzVyPUS3MlczPDZizszN M1HQc3NCVkeHUh?=
BT-549 M1fZO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4e0XWlEPTB;NEiuOVMyPSEQvF2= NYLaSG9IW0GQR1XS
LCLC-97TM1 NUjhXlUxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13UOWlEPTB;NEmuNlQyOyEQvF2= NGXDPHZUSU6JRWK=
A4-Fuk MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nhS2lEPTB;NEmuPFQ6KM7:TR?= Mn:yV2FPT0WU
OVCAR-4 M4jCbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTGT|BXUUN3ME21NE4xPjBzIN88US=> Mkm0V2FPT0WU
HD-MY-Z NFvtNYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXnMVndLUUN3ME21NE44PzZ2IN88US=> NFHsfYFUSU6JRWK=
NCI-H292 NIT2SmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYO4T2I6UUN3ME21NE45PzV6IN88US=> MnH0V2FPT0WU
Sk-ChA-1  MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYWySoZJOC5{NfMAl|UxKM7:TR?= MnP0O|IhcA>? Ml[xTWM2OD15ND61OOKyOi53ON88US=> NUS2[3B[OjV5NEK0PFI>
Mz-ChA-1 NEjnUYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{HVeFAvOjYkgKO1NEDPxE1? M4TxeVczKGh? MoXOTWM2OD13ND65O:KyOy52Nd88US=> NWjvPFhsOjV5NEK0PFI>
Smo-WT NHPwOGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVnRNYlOUUN3MNMgc4YhOTUEoH7N MlnrNlQzQTFzMES=
Smo-D473H  NEXIS5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;1emlEPTEEoH;mJFcvOcLizszN NFTqVG8zPDJ7MUGwOC=>
K562 MYjGeY5kfGmxbjDBd5NigQ>? MVmxNEDPxE1? M4DWSlczKGh? NIXBd3Jz\WS3Y3XzJJRp\SCneIDy[ZN{cW:wIH;mJGdtcTIEoB?= NXHRcmtQOjN|MUm4NlQ>
T315I BCR-ABL BaF3 NXvYNYc4TnWwY4Tpc44hSXO|YYm= NXfteod1OTBizszN NXrTe4JuPzJiaB?= NY[0epJ1emWmdXPld{B1cGViZYjwdoV{e2mxbjDv[kBIdGlzwrC= MnL3NlM{OTl6MkS=
TF-1 BCR-ABL NUfsboZyTnWwY4Tpc44hSXO|YYm= MX[xNEDPxE1? NV3NcHBQPzJiaB?= M{HhVpJm\HWlZYOgeIhmKGW6cILld5Nqd25ib3[gS4xqOcLi NETDTIozOzNzOUiyOC=>

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体内試験 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]

お薦めの試験操作(参考用のみ)

細胞試験: [2]
+ 展開
  • 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.
    (参考用のみ)
動物試験:[4]
+ 展開
  • 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
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 84 mg/mL (199.38 mM)
Water Insoluble
Ethanol Insoluble
体内 順序で溶剤を入れること:
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
10mg/mL

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 421.3
化学式

C19H14Cl2N2O3S

CAS No. 879085-55-9
保管
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03035188 Not yet recruiting Basal Cell Carcinoma SRH Wald-Klinikum Gera GmbH January 2017 Phase 2
NCT02956889 Recruiting Carcinoma, Basal Cell Istituto Clinico Humanitas October 2016 Phase 2
NCT02925234 Recruiting Cancer|Tumors|Neoplasm|Neoplasia The Netherlands Cancer Institute|Amgen|AstraZeneca|Bayer|Bristol-Myers Squibb|Novartis|Roche Pharma AG August 2016 Phase 2
NCT02366312 Active, not recruiting Keratocystic Odontogenic Tumor The Bluestone Center for Clinical Research|Genentech, Inc. June 2016 Phase 2
NCT02694224 Recruiting Breast Cancer Clinica Universidad de Navarra, Universidad de Navarra April 2016 Phase 2
NCT02693535 Recruiting Lymphoma, Non-Hodgkin|Multiple Myeloma|Advanced Solid Tumors American Society of Clinical Oncology|AstraZeneca|Bayer|Bristol-Myers Squibb|Eli Lilly and Company|Genentech, Inc.|Merck Sharp & Dohme Corp.|Pfizer March 2016 Phase 2

技術サポート

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。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

Hedgehog/Smoothened信号経路図

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID