Vismodegib-GDC-0449-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVismodegibCat. No.: HY-10440CAS No.: 879085-55-9Synonyms: GDC-0449分式: CHClNOS分量: 421.3作靶点: Hedgehog; Autophagy作通路: Stem Cell/Wnt; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50

2、 mg/mL (118.68 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.93 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.93 mM); Suspended solution; Need ultrasonic and warming3. 请依序添加每种溶剂： 10%

3、DMSO 90% corn oilSolubility: 2.5 mg/mL (5.93 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Vismodegib种可服的 hedgehog 抑制剂，IC50 值为 3 nM；同时可抑制 P-gp 和 ABCG2 的活性，IC50值分别为 3.0 M 和 1.4 M。IC50 & Target IC50: 3 nM (hedgehog), 3.0 M (P-gp), 1.4 M (ABCG2)体外研究 Vismodegib (HhAntag691) is an ABCG2 inhibitor and can inc

4、rease the effective intracellular concentration ofmitoxantrone, another ABCG2 substrate, through blocking its export in HEK293 cells. Vismodegib(HhAntag691, 10 M), resensitizes MDCKII/Pgp cells and MDCKII/MRP1 cells to colchicine treatment 2.Vismodegib (25 M or 50 M) concentration dependently inhibi

5、ts HCC and H1339 cells 3.体内研究 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 delayin patient-derived colorectal xenografts 4.PROTOCOLCe

6、ll Assay 2 When MTT assay is performed, an MTT reagent is added to each well to a final concentration of 150 g/mL,and the cells are incubated for 1 to 2 hours at 37C. The medium is then replaced with DMSO to dissolve thereaction product. Absorbance at 570 nm is quantified using a spectra MAX 340pc p

7、late reader. For the XTTassay, 1 mg/mL XTT is mixed with 0.025 mM PMS, and 50 L of the mixture is added to each well andincubated for 4 hours at 37C. After the plates are mixed on a plate shaker, absorbance at 450 nm ismeasured. All results are normalized to a percentage of absorbance obtained in co

8、ntrols.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Tumor-bearing mice are distributed into tumor volume-matched cohorts when the tumors reache betweenAdministration 2 200 and 350 mm3. The vismodegib-resistant medulloblastoma allograft, sg274,

9、 is developed by intermittentsuboptimal dosing of a Ptch+/, p53/medulloblastoma allograft. Vismodegib is formulated as a suspensionin 0.5% methyl-cellulose, 0.2% tween-80 (MCT), and is administered orally. Tumor volumes are determinedusing digital calipers using the formula (LWW)/2. Tumor growth inh

10、ibition (%TGI) is calculated as thepercentage of the area under the fitted curve (AUC) for the respective dose group per day in relation to thevehicle, such that %TGI=1001-(AUCtreatment/day)/(AUCvehicle/day).MCE has not independently confirmed the accuracy of these methods. They are for reference on

11、ly. J Control Release. 2019 Apr 17;303:77-90.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Cancer Lett. 2018 Apr 28;420:195-207. Oncogenesis. 2018 Mar 13;7(3):24. J Exp Clin Cancer Res. 2019 Sep 13;38(1):404. J Genet Genomics. 2018 May 20;45(5):237-246.See more customer validations on HYPERLINK

12、/ www.MedChemEREFERENCES1. 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),

13、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

14、of mutational and ligand-dependentHedgehog 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 ofSchistosoma-induced liver fibrosis. Parasitol Int. 2017 Oct;66(5):545-554.6. Ma W, et al. Reduced Smoothened level rescued A-induced memory deficits and neuronal inflammation in animal models ofAlzheimers disease. J Genet Genomics. 2018 May