1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETLR7 agonist 2Cat. No.: HY-103039CAS No.: 1642857-69-9分式: CHNO分量: 336.35作靶點(diǎn): Toll-like Receptor (TLR)作通路: Immunology/Inflammation儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 160 mg/mL (4

2、75.69 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.9731 mL 14.8655 mL 29.7309 mL5 mM 0.5946 mL 2.9731 mL 5.9462 mL10 mM 0.2973 mL 1.4865 mL 2.9731 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 TLR7 agonist 2種有效且有選擇性的 Toll 樣受體 7 (TLR7) 激動(dòng)

3、劑，LEC 值為 0.4 M。IC50 & Target LEC: 0.4 M (TLR7) 1體外研究TLR7 agonist 2 is a potent and selective Toll-like Receptor 7 (TLR7) agonist with a lowest effectiveconcentration (LEC) of 0.4 M in HEK293 cell. TLR7 agonist 2 is found to be selective for TLR7 over TLR8with LEC of 100 M for human TLR8. TLR7 agonis

4、t 2 demonstrates low inhibition across five CYP4501/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEisozymes (IC50 10 M) and is also not a time dependent inhibitor of CYP450 3A4. TLR7 agonist 2 haslimited inhibition of the hERG potassium ion channel 3H-dofetilide binding in vitro (IC50 50 M) 1.體內(nèi)研究 T

5、LR7 agonist 2 is found to be rapidly cleared in conjunction with our target profile. Both Cmax and AUCincrease less than dose proportionally between 0.3 and 3 mg/kg and more than dose-proportionally between3 and 10 mg/kg. TLR7 agonist 2 can induce an antiviral interferon stimulated gene (ISG) respon

6、se withoutinducing an IFN response at a low dose. TLR7 agonist 2 also induces a 2.7 log decrease in serum HBVviral load from 0.3 mg/kg, and a maximum 3.1 log decrease is observed for doses between 1 and 5 mg/kg1.PROTOCOLCell Assay 1 The ability of TLR7 agonist 2 to activate human TLR7 and/or TLR8 is

7、 assessed by using HEK293 cells.Briefly, HEK293 cells are grown in culture medium (DMEM supplemented with 10% FCS and 2 mMGlutamine). Transfected cells are then detached with Trypsin-EDTA, washed in PBS and resuspended inmedium to a density of 1.67105 cells/mL. Thirty microliters of cells are then d

8、ispensed into each well in 384-well plates, where 10 L of TLR7-agonist-1 in 4% DMSO is already present. Following 6 hours incubation at37C, 5% CO2, the luciferase activity is determined by adding 15 L of Steady Lite Plus substrate to eachwell and readout performed on a microplate imager. Lowest effe

9、ctive concentrations (LEC) values aredetermined for TLR7-agonist-1 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal A mouse in vivo model is used to demonstrate the initial proof of concept to induce endogenous IFN. SingleAdministration 1 oral a

10、dministration of 0.3, 1, 3, and 10 mg/kg doses of TLR7 agonist 2 is given to healthy, female, fastedC57Bl/6 mice. Concentrations of TLR7 agonist 2 and mouse-IFN via ELISA are measured from the plasmaand compare to vehicle 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. McGowan DC, et al. Identification and Optimization of Pyrrolo3,2-dpyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for theTreatment of Hepatitis B. J Med Chem. 2017 Jul 27;60(14):6137-6151.McePdfHeightCaution: Product has not bee