title: A Comprehensive Insight into the Chemical Space and ADME Features of Small Molecule NS5A Inhibitors.
abstract: Non-structural 5A (NS5A) protein plays a crucial role in the replication of hepatitis C virus (HCV) and during the past decade has attracted increasing attention as a promising biological target for the treatment of viral infections and related disorders. Small-molecule NS5A inhibitors have shown significant antiviral activity in vitro and in vivo. Several lead molecules are reasonably regarded as novel highly potent drug candidates with favorable ADME features and tolerable side effects. The first-in-class daclatasvir has recently been launched into the market and 14 novel molecules are currently under evaluation in clinical trials. From this perspective, we provide an overview of the available chemical space of small-molecule NS5A inhibitors and their PK properties, mainly focusing on the diversity in structure and scaffold representation.
authors.affiliation: Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny city, Moscow Region, 141700, Russia. yai@chemdiv.com.
authors.forename: Yan A
authors.initials: YA
authors.lastname: Ivanenkov
authors.forename: Mark S
authors.initials: MS
authors.lastname: Veselov
authors.forename: Artem G
authors.initials: AG
authors.lastname: Shakhbazyan
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Aladinskiy
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Aladinskaya
authors.forename: Sofya M
authors.initials: SM
authors.lastname: Yartseva
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Majouga
authors.forename: Anton S
authors.initials: AS
authors.lastname: Vantskul
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Leonov
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Ivachtchenko
authors.forename: Victor E
authors.initials: VE
authors.lastname: Koteliansky
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D054852:Small Molecule Libraries; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase