Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion.

Animals Antiviral Agents / chemical synthesis Benzimidazoles / chemical synthesis Biological Availability Cell Line, Tumor Clinical Trials as Topic Drug Discovery Humans Microbial Sensitivity Tests Protein Binding Respiratory Syncytial Virus, Human / drug effects Viral Fusion Proteins / metabolism Virus Internalization / drug effects

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
08 04 2021
Historique:
pubmed: 18 3 2021
medline: 8 6 2021
entrez: 17 3 2021
Statut: ppublish

Résumé

RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC

Identifiants

DOI: 10.1021/acs.jmedchem.0c01882 PMID: 33729773
pubmed: 33729773
doi: 10.1021/acs.jmedchem.0c01882
doi:

Substances chimiques

Antiviral Agents 0
Benzimidazoles 0
F protein, human respiratory syncytial virus 0
Viral Fusion Proteins 0
sisunatovir KE63TTO7WK

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3658-3676

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00001709
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT100544
Pays : United Kingdom

Auteurs

G Stuart Cockerill (GS)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.
ORCID: 0000-0002-6340-0808

Richard M Angell (RM)

Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.

Alexandre Bedernjak (A)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Irina Chuckowree (I)

Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.

Ian Fraser (I)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Jose Gascon-Simorte (J)

Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.

Morgan S A Gilman (MSA)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, United States.

James A D Good (JAD)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Rachel Harland (R)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Sara M Johnson (SM)

Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43205, United States.

John H Ludes-Meyers (JH)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, United States.

Edward Littler (E)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

James Lumley (J)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Graham Lunn (G)

Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.

Neil Mathews (N)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Jason S McLellan (JS)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, United States.

Michael Paradowski (M)

Medicines Discovery Institute, Cardiff University, Cardiff, Wales CF10 3AT, U.K.

Mark E Peeples (ME)

Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43205, United States.

Claire Scott (C)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Dereck Tait (D)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Geraldine Taylor (G)

The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, U.K.

Michelle Thom (M)

The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, U.K.

Elaine Thomas (E)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

Carol Villalonga Barber (C)

Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.

Simon E Ward (SE)

Medicines Discovery Institute, Cardiff University, Cardiff, Wales CF10 3AT, U.K.
ORCID: 0000-0002-8745-8377

Daniel Watterson (D)

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.

Gareth Williams (G)

Sussex Drug Discovery Centre, University of Sussex, Brighton, England BN1 9QJ, U.K.

Paul Young (P)

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.

Kenneth Powell (K)

Reviral Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2FX, U.K.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzimidazoles › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Pharmacocinétique › Biodisponibilité › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité microbienne › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Mononegavirales › Paramyxoviridae › Pneumovirinae › Pneumovirus › Virus respiratoires syncytiaux › Virus respiratoire syncytial humain › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de fusion virale › Discovery of Sisunatovir (RV521), an Inhibitor...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Pénétration virale › Discovery of Sisunatovir (RV521), an Inhibitor...