GDC-0449 (Vismodegib) |
| رقم الكتالوجGC10493 |
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 879085-55-9
Sample solution is provided at 25 µL, 10mM.
GDC-0449 (2-chloro-N-[4-chloro-3-pyridin-2-yl-phenyl]-4-methane-sulfonyl benzamide), discovered by high throughput screening of a small molecule compound library followed by subsequent optimization through medical chemistry, is a potent and selective inhibitor of hedgehog (Hh) signaling, a pathway regulating cell growth and differentiation associated in pathogenesis of several cancers. It binds to signaling by smoothened (SMO) and suppresses activation of downstream Hh target genes resulting in the inhibition of Hh signaling pathway. GDC-0449 exhibits anti-tumor activity in a mouse model of medulloblastoma as well as in primary human tumor cell xenograft models of colorectal cancer and pancreatic carcinoma and is currently being evaluated in research projects investigating refractory, locally advanced or metastatic solid tumors.
Reference
[1].Patricia M. LoRusso, Charles M. Rudin, Josina C. Reddy, Raoul Tibes, Glen J. Weiss, Mitesh J. Borad, Christine L. Hann, Julie R. Brahmer, Ilsung Chang, Walter C. Darbonne, Richard A. Graham, Kenn L. Zerivitz, Jennifer A. Low, and Daniel D. Von Hoff. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in Patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011; 17: 2502-2511
| Cell experiment: [1] | |
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Cell lines |
AsPC-1, MIA PaCa-2, PANC-1 and Pancreatic CSC cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 μM, 72 hours |
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Applications |
Inhibition of cell survival and induction of apoptosis was observed within 24 h following exposure to this drug, but was maximally noticed at 72 h. In all the cell lines, GDC-0449 induced apoptosis is a dose-dependent manner reaching up to 65%. By comparison, GDC-0449 was less effective in inducing apoptosis in CSCs. |
| Animal experiment: [2] | |
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Animal models |
Male CB17 SCID mice injected with MDA PCa 118b cells |
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Dosage form |
Oral administration, 100 mg/kg, twice a day for 21 days |
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Applications |
Shh, Gli1, Gli2, Smo, Ptch1, and Sufu were analyzed by qRT-PCR in GDC-0449 treated and untreated groups. Stromal expression of Gli1 and Ptch1 was marginally lower in the treated group compared to the control. Given that Gli1 and Ptch1 are reliable markers of an active Hh pathway these results confirm the pharmacodynamic effect of GDC-0449. Expression of Gli2 and Shh followed the same trend. Tumor epithelial expression of Sufu was significantly lower in treated than in untreated controls. Immunohistochemical testing confirmed a decrease in Sufu expression in the tumor epithelium. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Singh B N, Fu J, Srivastava R K, et al. Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One, 2011, 6(11): e27306. [2] Karlou M, Lu J F, Wu G, et al. Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC-0449 in the bone forming prostate cancer xenograft MDA PCa 118b. The Prostate, 2012, 72(15): 1638-1647. |
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| Cas No. | 879085-55-9 | SDF | |
| Chemical Name | 2-chloro-N-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide | ||
| Canonical SMILES | CS(=O)(=O)C1=CC(=C(C=C1)C(=O)NC2=CC(=C(C=C2)Cl)C3=CC=CC=N3)Cl | ||
| Formula | C19H14Cl2N2O3S | M.Wt | 421.3 |
| الذوبان | ≥ 21.1 mg/mL in DMSO, ≥ 4.96 mg/mL in EtOH with ultrasonic and warming | Storage | Desiccate at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3736 mL | 11.868 mL | 23.7361 mL |
| 5 mM | 0.4747 mL | 2.3736 mL | 4.7472 mL |
| 10 mM | 0.2374 mL | 1.1868 mL | 2.3736 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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