Presatovir-GS-5806-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPresatovirCat. No.: HY-16727CAS No.: 1353625-73-6Synonyms: GS-5806分式: CHClNOS分量: 532.06作靶點: RSV作通路: Anti-infection儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 6 mg/mL (11.28 mM; Need ult

2、rasonic and warming)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 0.6 mg/mL (1.13 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.6 mg/mL (1.13 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.

3、6 mg/mL (1.13 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Presatovir (GS-5806)新穎且有服活性的 RSV 融合抑制劑，平均EC50 值為0.43 nM。IC50 & Target EC50: 0.43 nM (RSV) 1體外研究 Presatovir is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimizationcampaign on a hit originated from a phenotyp

4、ic RSV antiviral high-throughput screen. Presatovir exhibitspotent activity against a wide range of RSV A and B clinical isolates with a mean EC50 value of 0.43 nM 1.GS-5806 inhibits pre to post triggered conformational changes of RSV F protein, suggesting a possiblemechanism for antiviral activity

5、2.體內(nèi)研究 Presatovir demonstrates dose-dependent (0-30 mg/kg) antiviral efficacy in a cotton rat model of RSVinfection. Oral bioavailability in preclinical species ranges from 46 to 100%, with penetration of the compoundinto the lung tissue demonstrated in Sprague-Dawley rats. Multidose oral treatment

6、of Presatovir appearssafe in adults, and in healthy human volunteers experimentally infected with RSV, a potent antiviral effectand reduction in disease severity is observed in the high dose group. A group treated with a lower dose ofPresatovir allows for a PK-PD relationship to be established to he

7、lp guide future dose selections 1.PROTOCOLCell Assay 1 GS-5806 are diluted in 100% DMSO. To conduct the cytopathic antiviral assay, 0.4 L of 100concentrated3-fold serially diluted drug is added to 20 L of cell culture medium in a 384-well plate. HEp-2 cells are thensuspended in MEM plus 10% FBS at a

8、 density of 1105 cells/mL, are infected in bulk with RSV A2 at a titerof approximately 1104.5 tissue culture infectious doses/mL. Immediately following infection, 20 L of RSV-infected cells are added to each well. The cells are then cultured for 4 days at 37 C. Following thisincubation the cells are

9、 allowed to equilibrate to 25C. The RSV-induced cytopathic effect is determined byadding 40 L of Cell-Titer Glo viability reagent. Following a 10 min incubation at 25 C, cell viability isdetermined 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品

10、發(fā)表的科研獻 J Antimicrob Chemother. 2018 Jul 1;73(7):1823-1829.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Mackman RL, et al. Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of

11、concept in ahuman RSV challenge study. J Med Chem. 2015 Feb 26;58(4):1630-1643.2. Samuel D, et al. GS-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein. AntimicrobAgents Chemother. 2015 Nov;59(11):7109-12.McePdfHeightCaution: Product has not be