Vemurafenib-PLX4032-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVemurafenibCat. No.: HY-12057CAS No.: 918504-65-1Synonyms: PLX4032; RG7204; RO5185426分式: CHClFNOS分量: 489.92作靶点: Raf; Autophagy作通路: MAPK/ERK Pathway; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month

2、溶解性数据体外实验 DMSO : 6.2 mg/mL (12.66 mM; Need ultrasonic and warming)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.10 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.10 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您

3、边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.10 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Vemurafenib (PLX4032; RG7204)是有效的 B-RAF 抑制剂，能够抑制 RAFV600E 和 c-RAF-1 的活性，IC50 分别为 31 nM 和 48 nM。IC50 & Target B-RafV600E c-Raf-131 nM (IC50) 48 nM (IC50)体外研究 Vemurafenib (PLX4032

4、) selectively blocks the RAF/MEK/ERK pathway in BRAF mutant cells 1. RG7204 isa potent inhibitor of proliferation in those expressing RAFV600E but not BRAFWT in 17 melanoma cell lines.Vemurafenib (RG7204) induces MEK and ERK phosphorylation at high concentrations in CHL-1 cells 2.Ectopic expression

5、of EGFR in melanoma cells is sufficient to cause resistance to PLX4032 3.体内研究 Vemurafenib (PLX4032, 20, 25, 75 mg/kg, p.o.) causes dose-dependent inhibition of tumor growth, withhigher exposures resulting in tumor regression of BRAF mutant xenografts 1. RG7204 (12.5, 25, and 75mg/kg, p.o.) significa

6、ntly inhibits tumor growth and induced tumor regression in mice bearing LOX tumorxenografts 2.PROTOCOLCell Assay 2 Briefly, cells are plated in 96-well microtiter plates at a density of 1,000 to 5,000 cells per well in a volume of180 L. For the assay, Vemurafenib (RG7204) is prepared at 10 times the

7、 final assay concentration in mediacontaining 1% DMSO. Twenty-four hours after cell plating, 20 L of the appropriate dilution are added toplates in duplicate. The plates are assayed for proliferation 6 days after the cells are plated according to theprocedure.MCE has not independently confirmed the

8、accuracy of these methods. They are for reference only.Animal Athymic nude mice, are with ages 13 to 14 weeks, and weighing approximately 23 to 25 g. For the LOXAdministration 2 xenografts, 2106 cells in 0.2 mL of PBS are injected s.c. into the right lateral flank. Vemurafenib (RG7204),formulated as

9、 MBP, is suspended at the desired concentration as needed for each dose group in an aqueousvehicle containing 2% Klucel LF and adjusted to pH 4 with dilute HCl. NSC 362856 is of 250-mg capsules.Capsules are opened and combined into one bulk supply. To prepare the stock dosing material, NSC 362856is

10、first dissolved in 100% DMSO followed by dilution with saline to form a final milky white suspension in 10%DMSO/90% saline (pH 3.4).MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.2/3 Master

11、 of Small Molecules 您边的抑制剂师www.MedChemE Sci Adv. 2019 Aug. Nat Commun. 2015 Sep 24;6:8390. Mol Syst Biol. 2017 Jan; 13(1): 905. Mol Syst Biol. 2015 Mar 26;11(3):797.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Bollag G, et al. Clinical efficacy of a RAF inhibitor needs broad

12、 target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315),596-599.2. Yang H, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models.Cancer Res, 2010, 70(13), 5518-5527.3. Prahallad A, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature, 2012,483(7387), 100-103.McePdfHeightCauti