2. Academic Validation
  3. Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms

Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms

  • J Med Chem. 2017 Jan 12;60(1):290-306. doi: 10.1021/acs.jmedchem.6b01310.
Ling Tong,  Wensheng Yu,  Lei Chen,  Oleg Selyutin,  Michael P Dwyer,  Anilkumar G Nair,  Robert Mazzola,  Jae-Hun Kim,  Deyou Sha,  Jingjun Yin,  Rebecca T Ruck,  Ian W Davies,  Bin Hu 1,  Bin Zhong 1,  Jinglai Hao 1,  Tao Ji 1,  Shuai Zan 1,  Rong Liu,  Sony Agrawal,  Ellen Xia,  Stephanie Curry,  Patricia McMonagle,  Karin Bystol,  Frederick Lahser,  Donna Carr,  Laura Rokosz,  Paul Ingravallo,  Shiying Chen,  Kung-I Feng,  Mark Cartwright,  Ernest Asante-Appiah,  Joseph A Kozlowski
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China.
PMID: 27808515 DOI: 10.1021/acs.jmedchem.6b01310
Abstract

We describe the research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a "flat" GT1 mutant profile. This NS5A inhibitor contains a unique tetracyclic indole core while maintaining the imidazole-proline-valine Moc motifs of our previous NS5A inhibitors. Compound 40 is currently in early clinical trials and is under evaluation as part of an all-oral DAA regimen for the treatment of chronic HCV Infection.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101663
    HCV NS5A Inhibitor
    HCV