CAS 879085-55-9|vismodegib(GDC-0449)
| Common Name | vismodegib(GDC-0449) | ||
|---|---|---|---|
| CAS Number | 879085-55-9 | Molecular Weight | 421.297 |
| Density | 1.4±0.1 g/cm3 | Boiling Point | 561.6±50.0 °C at 760 mmHg |
| Molecular Formula | C19H14Cl2N2O3S | Melting Point | / |
| MSDS | / | Flash Point | 293.4±30.1 °C |
Names
| Name | vismodegib |
|---|---|
| Synonym | More Synonyms |
vismodegib(GDC-0449) BiologicalActivity
| Description | Vismodegib (GDC-0449) is an orally active hedgehog pathway inhibitor with an IC50 of 3 nM. It also inhibits P-gp, ABCG2 with IC50 values of 3.0 μM and 1.4 μM, respectively. |
|---|---|
| Related Catalog | Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Stem Cell/Wnt >>HedgehogResearch Areas >>Cancer |
| Target | IC50: 3 nM (hedgehog), 3.0 μM (P-gp), 1.4 μM (ABCG2) |
| In Vitro | Vismodegib (HhAntag691) is an ABCG2 inhibitor and can increase the effective intracellular concentration of mitoxantrone, another ABCG2 substrate, through blocking its export in HEK293 cells. Vismodegib (HhAntag691, 10 µM), resensitizes MDCKII/Pgp cells and MDCKII/MRP1 cells to colchicine treatment[2]. Vismodegib (25 μM or 50 μM) concentration dependently inhibits HCC and H1339 cells[3]. |
| In Vivo | Vismodegib is a novel small molecule HPI, often used for clinical trials[1]. Vismodegib (0.3 to 75 mg/kg, p.o.) is highly efficacious in medulloblastoma allograft tumors. Vismodegib (> 46 mg/kg, p.o.) causes growth delay in patient-derived colorectal xenografts[4]. |
| Cell Assay | When MTT assay is performed, an MTT reagent is added to each well to a final concentration of 150 µg/mL, and the cells are incubated for 1 to 2 hours at 37°C. The medium is then replaced with DMSO to dissolve the reaction product. Absorbance at 570 nm is quantified using a spectra MAX 340pc plate reader. For the XTT assay, 1 mg/mL XTT is mixed with 0.025 mM PMS, and 50 µL of the mixture is added to each well and incubated for 4 hours at 37°C. After the plates are mixed on a plate shaker, absorbance at 450 nm is measured. All results are normalized to a percentage of absorbance obtained in controls. |
| Animal Admin | Tumor-bearing mice are distributed into tumor volume-matched cohorts when the tumors reache between 200 and 350 mm3. The vismodegib-resistant medulloblastoma allograft, sg274, is developed by intermittent suboptimal dosing of a Ptch+/−, p53−/−medulloblastoma allograft. Vismodegib is formulated as a suspension in 0.5% methyl-cellulose, 0.2% tween-80 (MCT), and is administered orally. Tumor volumes are determined using digital calipers using the formula (L×W×W)/2. Tumor growth inhibition (%TGI) is calculated as the percentage of the area under the fitted curve (AUC) for the respective dose group per day in relation to the vehicle, such that %TGI=100×1-(AUCtreatment/day)/(AUCvehicle/day). |
| References | [1]. Scales SJ, et al. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci. 2009, 30(6), 303-312. [2]. Zhang Y, et al. Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp. Neoplasia. 2009, 11(1), 96-101. [3]. Tian F, et al. The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. Anticancer Res. 2012, 32(1), 89-94. [4]. Wong H, et al. Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation. Clin Cancer Res. 2011, 17(14), 4682-4692. [5]. Elhenawy AA, et al. Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma-induced liver fibrosis. Parasitol Int. 2017 Oct;66(5):545-554. [6]. Ma W, et al. Reduced Smoothened level rescued Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease. J Genet Genomics. 2018 May 20;45(5):237-246. |
Chemical & Physical Properties
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 561.6±50.0 °C at 760 mmHg |
| Molecular Formula | C19H14Cl2N2O3S |
| Molecular Weight | 421.297 |
| Flash Point | 293.4±30.1 °C |
| Exact Mass | 420.010223 |
| PSA | 84.51000 |
| LogP | 2.98 |
| Vapour Pressure | 0.0±1.5 mmHg at 25°C |
| Index of Refraction | 1.641 |
| InChIKey | BPQMGSKTAYIVFO-UHFFFAOYSA-N |
| SMILES | CS(=O)(=O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1 |
Safety Information
| HS Code | 2933399090 |
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Customs
| HS Code | 2933399090 |
|---|---|
| Summary | 2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |
Synonyms
| vismodegib |
| 2-Chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide |
| GDC-0449 |
| GDC0449 |
