GNE-6776 _Deubiquitinase 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGNE-6776Cat. No.: HY-107986CAS No.: 2009273-71-4分式: CHNO分量: 348.4作靶点: Deubiquitinase作通路: Cell Cycle/DNA Damage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 : 310 mg/mL (889.78 mM)* means so

2、luble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.8703 mL 14.3513 mL 28.7026 mL5 mM 0.5741 mL 2.8703 mL 5.7405 mL10 mM 0.2870 mL 1.4351 mL 2.8703 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 GNE-6776种选择性 USP7 抑制剂。IC50 & Target USP7 1体外研究GNE-67

3、76 non-covalently targets USP7 12 distant from the catalytic cysteine. GNE-6776 attenuatesubiquitin binding and thus inhibits USP7 deubiquitinase activity. GNE-6776 interacts with acidic residues that1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEmediate hydrogen-bond interactions with the ubiquit

4、in Lys48 side chain. GNE-6776 targets cellular USP7,MDM2, and p53 signalling pathways.GNE-6776 selectively inhibits recombinant USP7 relative to 36 otherdeubiquitinases. GNE-6776 remains selective even at 100M, a more than sixfold higher concentration thanused in cellular assays. GNE-6776 significan

5、tly inhibits USP7 while remaining selective against 44-47 otherdetected deubiquitinases 1.体内研究 Although efficacious exposure is only transiently achieved, GNE-6776 causes modest, although significant,EOL-1 xenograft growth delay 1.PROTOCOLCell Assay 1 EOL-1 cells are seeded into 384-well plates 24h

6、before compound addition. Cells are then incubated withcompound (e.g., GNE-6776; 0.003, 0.009, 0.027, 0.082, 0.25, 0.74, 2.22, 6.67, and 20 M) for 72h or 120hbefore assaying viability. Assays are performed in biological triplicate. Cells are incubated (37C, 5% CO2) inRPMI-1640, 2.5% FBS (72h assay)

7、or 5% FBS (120h assay), and 2mM glutamine throughout the assay.The reported IC50 and mean viability metrics are as follows: IC50 is the dose at which the estimatedinhibition is 50% relative to untreated wells (that is, absolute IC50). The mean viability is calculated 1.MCE has not independently conf

8、irmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 GNE-6776 is administered at 200mg/kg (body weight) by oral gavage to female C.B-17 SCID mice, aged 12-16 weeks (n=3 per time point). No randomization is used for DMPK studies. At 0.5, 1, 2, 4, 8 and 24h po

9、st-dose, blood samples are collected by terminal cardiac puncture into anticoagulant tubes (EDTA). Clarifiedplasma is then transferred to a fresh tube and snap frozen. GNE-6776 plasma concentrations are determinedby LC-MS/MS 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Kategaya L, et al. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017 Oct 26;550(7677):534-538.McePdfHeightCaution: Product has not been fully validated f