2-Substituted α,β-Methylene-ADP Derivatives: Potent Competitive Ecto-5'-nucleotidase (CD73) Inhibitors with Variable Binding Modes.

5'-Nucleotidase / antagonists & inhibitors Adenosine Diphosphate / analogs & derivatives Animals Crystallography, X-Ray Enzyme Inhibitors / chemistry GPI-Linked Proteins / antagonists & inhibitors Humans Molecular Docking Simulation Protein Binding Rats Structure-Activity Relationship

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:
26 03 2020
Historique:
pubmed: 12 2 2020
medline: 4 9 2020
entrez: 12 2 2020
Statut: ppublish

Résumé

CD73 inhibitors are promising drugs for the (immuno)therapy of cancer. Here, we present the synthesis, structure-activity relationships, and cocrystal structures of novel derivatives of the competitive CD73 inhibitor α,β-methylene-ADP (AOPCP) substituted in the 2-position. Small polar or lipophilic residues increased potency, 2-iodo- and 2-chloro-adenosine-5'-

Identifiants

DOI: 10.1021/acs.jmedchem.9b01611 PMID: 32045236
pubmed: 32045236
doi: 10.1021/acs.jmedchem.9b01611
doi:

Substances chimiques

Enzyme Inhibitors 0
GPI-Linked Proteins 0
alpha,beta-methyleneadenosine 5'-diphosphate 0T2A5439OE
Adenosine Diphosphate 61D2G4IYVH
5'-Nucleotidase EC 3.1.3.5
NT5E protein, human EC 3.1.3.5

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2941-2957

Auteurs

Sanjay Bhattarai (S)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Jan Pippel (J)

Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Leipzig University, Deutscher Platz 5, D-04103 Leipzig, Germany.

Emma Scaletti (E)

Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Leipzig University, Deutscher Platz 5, D-04103 Leipzig, Germany.

Riham Idris (R)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Marianne Freundlieb (M)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Georg Rolshoven (G)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Christian Renn (C)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Sang-Yong Lee (SY)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Aliaa Abdelrahman (A)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Herbert Zimmermann (H)

Institute of Cell Biology and Neuroscience, Goethe-University, D-60438 Frankfurt am Main, Germany.

Ali El-Tayeb (A)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

Christa E Müller (CE)

PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
ORCID: 0000-0002-0013-6624

Norbert Sträter (N)

Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Leipzig University, Deutscher Platz 5, D-04103 Leipzig, Germany.
ORCID: 0000-0002-2001-0500

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Phosphoric monoester hydrolases › Nucleotidases › 5'-Nucleotidase › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › ADP › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Eucaryotes › Animaux › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de docking moléculaire › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › 2-Substituted α,β-Methylene-ADP Derivatives:...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › 2-Substituted α,β-Methylene-ADP Derivatives:...