5-Phenyl-1,3,4-oxadiazol-2(3

Administration, Oral Animals Binding Sites Blood-Brain Barrier / drug effects Crystallography, X-Ray Drug Design Enzyme Inhibitors / chemistry Esterases / antagonists & inhibitors Half-Life Humans Inhibitory Concentration 50 Male Mice Mice, Inbred C57BL Microsomes, Liver / metabolism Molecular Dynamics Simulation Oxadiazoles / chemistry Structure-Activity Relationship Wnt Signaling Pathway / 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:
12 11 2020
Historique:
pubmed: 31 10 2020
medline: 19 12 2020
entrez: 30 10 2020
Statut: ppublish

Résumé

Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole

Identifiants

DOI: 10.1021/acs.jmedchem.0c01391 PMID: 33124429
pubmed: 33124429
doi: 10.1021/acs.jmedchem.0c01391
doi:

Substances chimiques

Enzyme Inhibitors 0
Oxadiazoles 0
Esterases EC 3.1.-
Notum protein, human EC 3.1.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12942-12956

Subventions

Organisme : Cancer Research UK
ID : FC001002
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001002
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001002
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C375/A17721
Pays : United Kingdom

Auteurs

William Mahy (W)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.

Nicky J Willis (NJ)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.

Yuguang Zhao (Y)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.
ORCID: 0000-0001-8916-8552

Hannah L Woodward (HL)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.
ORCID: 0000-0001-8429-2546

Fredrik Svensson (F)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.
The Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.
ORCID: 0000-0002-5556-8133

James Sipthorp (J)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.
The Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.

Luca Vecchia (L)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.

Reinis R Ruza (RR)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.

James Hillier (J)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.

Svend Kjær (S)

The Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.

Sarah Frew (S)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.

Amy Monaghan (A)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.

Magda Bictash (M)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.

Patricia C Salinas (PC)

Department of Cell and Developmental Biology, Laboratory for Molecular and Cellular Biology, University College London, London WC1E 6BT, U.K.

Paul Whiting (P)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.

Jean-Paul Vincent (JP)

The Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.

E Yvonne Jones (EY)

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, U.K.

Paul V Fish (PV)

Alzheimer's Research UK UCL Drug Discovery Institute, University College London, Cruciform Building, Gower Street, London WC1E 6BT, U.K.
The Francis Crick Institute, 1 Midland Road, Kings Cross, London NW1 1AT, U.K.
ORCID: 0000-0002-2117-2173

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie orale › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Eucaryotes › Animaux › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Barrière hémato-encéphalique › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Conception de médicament › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Phénomènes physiques › Temps › Période › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Concentration inhibitrice 50 › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Microsomes › Microsomes du foie › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de dynamique moléculaire › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Oxazoles › Oxadiazoles › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › 5-Phenyl-1,3,4-oxadiazol-2(3
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › 5-Phenyl-1,3,4-oxadiazol-2(3