AGI-5198-IDH-C35-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAGI-5198Cat. No.: HY-18082CAS No.: 1355326-35-0Synonyms: IDH-C35分式: CHFNO分量: 462.56作靶点: Isocitrate Dehydrogenase (IDH)作通路: Metabolic Enzyme/Protease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

2、DMSO : 34 mg/mL (73.50 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1619 mL 10.8094 mL 21.6188 mL5 mM 0.4324 mL 2.1619 mL 4.3238 mL10 mM 0.2162 mL 1.0809 mL 2.1619 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AGI-5198是有效和选择性的

3、突变体 IDH1R132H 抑制剂，IC50 为0.07 M。体外研究Measurements of R-2HG concentrations in pellets of TS603 glioma cells demonstrates dose-dependentinhibition of the mutant IDH1 enzyme by AGI-5198. AGI-5198 does not impair colony formation of twopatient-derived glioma lines that express only the wild-type IDH1 alle

4、le (TS676 and TS516) 1. Cancer cells1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEheterozygous for the IDH1(R132H) mutation exhibits less IDH-mediated production of NADPH, such thatafter exposure to ionizing radiation (IR), there are higher levels of reactive oxygen species, DNA double-strand bre

5、aks, and cell death compared with IDH1 wild-type cells. These effects are reversed by theIDH1(R132H) inhibitor AGI-5198 2.体内研究 AGI-5198 (450 mg/kg, p.o.) causes 50 to 60% growth inhibition of the tumor growth from human gliomaxenografts. Tumors from AGI-5198- treated mice show reduced staining with

6、an antibody against the Ki-67protein. AGI-5198 does not affect the growth of IDH1 wild-type glioma xenografts 1.PROTOCOLKinase Assay 1 Inhibitory potency against the IDH2 R140Q and IDH2 R172K enzymes is determined in an endpoint assay inwhich the amount of NADPH remaining at the end of the reaction

7、is measured by the addition of a largeexcess of diaphorase and resazurin. IDH2 R140Q is diluted to 0.25 g/mL in 40 L 1X Assay Buffer (150 mMNaCl, 50 mM potassium phosphate pH 7.5, 10 mM MgCl2, 10% glycerol, 2 mM B-ME, 0.03% BSA) andincubated for 16 hours at 25C in the presence of 1 L of compound in

8、DMSO. The reaction is started withthe addition of 10 L of Substrate Mix (20 M NADPH, 8 M alpha-ketoglutarate, in 1X Assay Buffer) andincubated for 1 hour at 25C. Then, remaining NADPH is measured by the addition of 25 L of Detection Mix(36 g/mL diaphorase, 18 M resazurin in 1X Assay buffer), incubat

9、ed for 5 minutes at 25C, and read asdescribed above. IDH2 R172K is assayed as for IDH2 R140Q with the following modifications: 1.25 g/mL ofprotein is used, the Substrate Mix contained 50 M NADPH and 6.4 M alpha-ketoglutarate, and thecompound is incubated for 1 hour before starting the reaction.MCE h

10、as not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 TS603 cells are grown in medium containing either AGI-5198 (1.5M) or DMSO vehicle control. One weekprior to harvest cells are ransferred to differentiation medium (DMEM F12; 15 mM HEPES; 0.06% gluc

11、ose;B27 without vitamin A; N2; Insulin/transferrin; 1% FBS) containing freshly added retinoic acid (1M). ChIP ofnon-crosslinked cells is then carried out using established ChIP methods. 350 g of lysate isimmunoprecipitated-using anti-H3K9Me3, H3K27me3 or Rabbit Control IgG. After washing, ChIP DNA i

12、seluted from protein G beads and analyzed by RT-PCR using SYBR green. Relative occupancy is calculatedusing the standard curve method and fold enrichment versus IgG. Enrichment in AGI- 5198-treated cells isnormalized to vehicle control. Means and standard deviation are calculated from 4 technical re

13、plicates.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal SCID mice are injected subcutaneously with 106 glioma cells, which are suspended in 100 L of a 50:50Administration 1 mixture of growth media and Matrigel. Once tumors have reached a measura

14、ble size, mice are randomizedinto the indicated treatment groups.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 Clin Cancer Res. 2018 Apr 1;24(7):1705-1715. Cancer Res. 2018 Nov 15;78(22):6386-6398.2/3 Master of Small Molecules 您边的抑制剂师www.M

15、edChemE Cancer Res. 2015 Nov 15;75(22):4790-802. FASEB J. 2018 Jun 7:fj201800547R. ACS Med Chem Lett. 2015 Jun 22;6(8):948-52.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Rohle D, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013 May3;340(6132):626-30.2. Molenaar RJ, et al. Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198. Cancer