SCH772984-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESCH772984Cat. No.: HY-50846CAS No.: 942183-80-4分式: CHNO分量: 587.67作靶点: ERK作通路: MAPK/ERK Pathway; Stem Cell/Wnt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 : 14.29 mg/mL (24.32 mM; Need ultr

2、asonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.43 mg/mL (2.43 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.43 mg/mL (2.43 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolu

3、bility: 1.43 mg/mL (2.43 mM); Clear solution4. 请依序添加每种溶剂： 20% SBE-CD adjusted to pH 4-4.5 with 1 N aceticSolubility: 20 mg/mL (34.03 mM); Clear solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性 SCH772984 有效抑制 ERK1 和 ERK2 活性，IC50 分别为 4 和 1 nM。IC50 & Target ERK2 ERK11 nM (IC50) 4 nM (IC50)体外研究 SCH772984

4、 shows EC50 values less than 500 nM in approximately 88% and 49% of BRAF-mutant (n=25) orRAS-mutant (n=35) tumor lines, respectively. Flow cytometric analysis of SCH772984-sensitive melanomacells revealed a G1 arrest as well as an increase in the sub-G1 fraction indicative of apoptosis. Less than20%

5、 of cells wild-type for both RAS and BRAF (n=61) are sensitive to SCH772984 1.体内研究 Treatment of BRAF-mutant LOX melanoma xenografts with SCH772984 (50 mg/kg twice daily) leads to 98%tumor regression. Dose-dependent antitumor activity is also observed in the KRAS-mutant pancreaticMiaPaCa model, with

6、36% regression at 50 mg/kg twice daily. Importantly, tumor regression is accompaniedby robust inhibition of ERK phosphorylation in tumor tissue. SCH772984 is well tolerated on this schedule asmeasured by morbidity, lethality, or body weight loss 1.PROTOCOLKinase Assay 1 SCH772984 is tested in 8-poin

7、t dilution curves in duplicate against purified ERK1 or ERK2. The enzyme isadded to the reaction plate and incubated with the compound before adding a solution of substrate peptideand ATP. Fourteen microliters of diluted enzyme (0.3 ng active ERK2 per reaction) is added to each well of a384-well pla

8、te. The plates are gently shaken to mix the reagents and incubated for 45 minutes at roomtemperature. The reaction is stopped with 60 L of IMAP Binding Solution (1:2,200 dilutions of IMAP beads in1 binding buffer). The plates are incubated at room temperature for an additional 0.5 hours to allowcomp

9、lete binding of phosphopeptides to the IMAP beads. Plates are read on the LJL Analyst 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cell proliferation experiments are carried out in a 96-well format (six replicates), and the BRAFV600E-m

10、utanthuman melanoma cell line LOXIMV1 (LOX) are plated at a density of 4,000 cells per well. At 24 hours aftercell seeding, cells are treated with DMSO or a 9-point IC50 dilution (0.001-10 M) at a final concentration of1% DMSO for all concentrations. Viability is assayed 5 days after dosing using th

11、e ViaLight luminescence kit.For the cell line panel viability assay, cells are treated with SCH772984 for 4 days and assayed by theCellTiterGlo luminescent cell viability assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 12/3 Master of

12、 Small Molecules 您边的抑制剂师www.MedChemEAdministration 1 Nude mice are injected subcutaneously with specific cell lines, grown to approximately 100 mm3,randomized to treatment groups (10 mice/group), and treated intraperitoneally with either SCH772984 (12.5,25, or 50 mg/kg) or vehicle. Tumor length (L),

13、 width (W), and height (H) are measured during and after thetreatment periods by a caliper twice weekly on each mouse and then used to calculate tumor volume usingthe formula (LWH)/2. Animal body weights are measured on the same days twice weekly. Uponcompletion of the experiment, vehicle- and SCH77

14、2984-treated tumor biopsies are processed for Westernblot analysis.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. Cancer Res. 2018 Feb 15;78(4):891-908. Theranostics. 2018 Jul 30;8(15):4262-4278. Haematologica. 2019 Jul 9. Elife. 2016 Nov 15;5. pii: e18489.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Morris EJ, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. CancerDiscov