Vismodegib (GDC-0449)

Catalog No.S1082

Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM in a cell-free assay.

Price Stock Quantity  
USD 144 In stock
USD 90 In stock
USD 170 In stock
USD 370 In stock
USD 970 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Vismodegib (GDC-0449) Chemical Structure

Vismodegib (GDC-0449) Chemical Structure
Molecular Weight: 421.3

Validation & Quality Control

Cited by 33 publications:

15 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Vismodegib (GDC-0449) is available in the following compound libraries:

Hedgehog/Smoothened Inhibitors with Unique Features

  • Selective Smoothened inhibitor

    PF-5274857 Smoothened-selective, IC50=5.8 nM.

  • Smoothened Inhibitor in Clinical Trial

    LDE225 (NVP-LDE225,Erismodegib) Phase III for Hh-pathway activated relapsed Medulloblastoma (MB).

  • Newest Smoothened Inhibitor

    GANT61 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.

  • Smoothened Activator

    Purmorphamine Directly binds and activates Smoothened, and blocks BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM.

Product Information

  • Compare Hedgehog/Smoothened Inhibitors
    Compare Hedgehog/Smoothened Products
  • Research Area

Product Description

Biological Activity

Description Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM in a cell-free assay.
Targets Hedgehog [1]
(Cell-free assay)
IC50 3 nM
In vitro 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
Smo-D473H NHLYN3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1\qd2lEPTEEoH;mJFcvOcLizszNMknRNlQzQTFzMES=
T315I BCR-ABL BaF3MVHGeY5kfGmxbjDBd5NigQ>?NH;kRZgyOCEQvF2=M1rySlczKGh?MVvy[YR2[2W|IITo[UBmgHC{ZYPzbY9vKG:oIFfsbVHDqA>?NYO4NmQ6OjN|MUm4NlQ>
TF-1 BCR-ABLMmfVSpVv[3Srb36gRZN{[Xl?NVvuNYk6OTBizszNMljiO|IhcA>?M{jiVZJm\HWlZYOgeIhmKGW6cILld5Nqd25ib3[gS4xqOcLiNGnsRWgzOzNzOUiyOC=>

... Click to View More Cell Line Experimental Data

In vivo 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]

Protocol(Only for Reference)

Cell Assay: [2]

Cell lines MDCKII cells
Concentrations 20 μM
Incubation Time 2 hours
Method 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.

Animal Study: [4]

Animal Models Ptch(+/-) allograft model, D5123 and 1040830
Formulation In 0.5% methyl-cellulose, 0.2% tween-80
Dosages ~ 100 mg/kg
Administration Orally

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

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor36128520
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] Scales SJ, et al. Trends Pharmacol Sci. 2009, 30(6), 303-312.

[2] Zhang Y, et al. Neoplasia. 2009, 11(1), 96-101.

view more

Clinical Trial Information( data from, updated on 2016-07-23)

NCT Number Recruitment Conditions Sponsor
Start Date Phases
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|B  ...more 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
NCT02690948 Recruiting Skin Basal Cell Carcinoma Anne Chang|Merck Sharp & Dohme Corp.|National Cancer Inst  ...more Anne Chang|Merck Sharp & Dohme Corp.|National Cancer Institute (NCI)|Stanford University February 2016 Phase 2
NCT02366312 Recruiting Keratocystic Odontogenic Tumor The Bluestone Center for Clinical Research|Genentech, Inc. January 2016 Phase 2
NCT02648048 Recruiting Idiopathic Pulmonary Fibrosis Hoffmann-La Roche January 2016 Phase 1

view more

Chemical Information

Download Vismodegib (GDC-0449) SDF
Molecular Weight (MW) 421.3


CAS No. 879085-55-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 84 mg/mL (199.38 mM)
Water <1 mg/mL (<1 mM)
Ethanol <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.
Chemical Name 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide

Customer Product Validation(15)

Click to enlarge
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
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
Source Gut 2013 62, 299-309. Vismodegib (GDC-0449) purchased from Selleck
Method Immunohistochemistry
Cell Lines Mdr2 -/- mice/hepatectomised mice
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
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
Source Cancer Res 2014 72, 5912-20. Vismodegib (GDC-0449) purchased from Selleck
Method Western blot/Immunohistochemistry
Cell Lines Twelve-month-old mice
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
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
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
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
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
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
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
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
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
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
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.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Hedgehog/Smoothened Products

  • Smoothened Agonist (SAG) HCl

    Smoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.

  • 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.

  • Cyclopamine

    Cyclopamine is a specific Hedgehog (Hh) signaling pathway antagonist of Smoothened (Smo) with IC50 of 46 nM in TM3Hh12 cells.

  • GANT61

    GANT61 is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, 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 in HEK293T cell and also is an inducer of osteoblast differentiation with EC50 of 1 μM.

  • LDE225 (NVP-LDE225,Erismodegib)

    LDE225 (NVP-LDE225,Erismodegib) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.

  • Taladegib (LY2940680)

    Taladegib (LY2940680) binds to the Smoothened (Smo) receptor and potently inhibits Hedgehog (Hh) signaling. Phase 1/2.

  • Glasdegib (PF-04449913)

    Glasdegib (PF-04449913) is a potent, and orally bioavailable Smoothened (Smo) inhibitor with IC50 of 5 nM. Phase 2.

  • SANT-1

    SANT-1 directly binds to Smoothened (Smo) receptor with Kd of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 nM.

    Features:Attenuates SAG stimulation of Shh-LIGHT2 cells to a greater extent relative to other antagonists.

Recently Viewed Items

Tags: buy Vismodegib (GDC-0449) | Vismodegib (GDC-0449) ic50 | Vismodegib (GDC-0449) price | Vismodegib (GDC-0449) cost | Vismodegib (GDC-0449) solubility dmso | Vismodegib (GDC-0449) purchase | Vismodegib (GDC-0449) manufacturer | Vismodegib (GDC-0449) research buy | Vismodegib (GDC-0449) order | Vismodegib (GDC-0449) mouse | Vismodegib (GDC-0449) chemical structure | Vismodegib (GDC-0449) mw | Vismodegib (GDC-0449) molecular weight | Vismodegib (GDC-0449) datasheet | Vismodegib (GDC-0449) supplier | Vismodegib (GDC-0449) in vitro | Vismodegib (GDC-0449) cell line | Vismodegib (GDC-0449) concentration | Vismodegib (GDC-0449) nmr
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us