2. Academic Validation
  3. Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study

Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study

  • J Med Chem. 2015 Feb 26;58(4):1630-43. doi: 10.1021/jm5017768.
Richard L Mackman 1,  Michael Sangi,  David Sperandio,  Jay P Parrish,  Eugene Eisenberg,  Michel Perron,  Hon Hui,  Lijun Zhang,  Dustin Siegel,  Hai Yang,  Oliver Saunders,  Constantine Boojamra,  Gary Lee,  Dharmaraj Samuel,  Kerim Babaoglu,  Anne Carey,  Brian E Gilbert,  Pedro A Piedra,  Robert Strickley,  Quynh Iwata,  Jaclyn Hayes,  Kirsten Stray,  April Kinkade,  Dorothy Theodore,  Robert Jordan,  Manoj Desai,  Tomas Cihlar
Affiliations

Affiliation

  • 1 Gilead Sciences , 333 Lakeside Drive, Foster City, California 94404, United States.
PMID: 25574686 DOI: 10.1021/jm5017768
Abstract

GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a screening hit. The oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. A mean EC50 = 0.43 nM was found toward a panel of 75 RSV A and B clinical isolates and dose-dependent Antiviral efficacy in the cotton rat model of RSV Infection. Oral bioavailability in preclinical species ranged from 46 to 100%, with evidence of efficient penetration into lung tissue. In healthy human volunteers experimentally infected with RSV, a potent Antiviral effect was observed with a mean 4.2 log10 reduction in peak viral load and a significant reduction in disease severity compared to placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV Infection in infants and adults is reported.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16727
    99.91%, RSV Fusion 抑制剂
    RSV
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