Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach.

1-Alkyl-2-acetylglycerophosphocholine Esterase / antagonists & inhibitors Boron Compounds / chemistry Cysteine / chemistry Drug Discovery Enzyme Inhibitors / chemistry HEK293 Cells Humans Models, Molecular Molecular Conformation

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:
09 07 2020
Historique:
pubmed: 28 5 2020
medline: 18 11 2020
entrez: 28 5 2020
Statut: ppublish

Résumé

Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound

Identifiants

DOI: 10.1021/acs.jmedchem.0c00372 PMID: 32459096
pubmed: 32459096
doi: 10.1021/acs.jmedchem.0c00372
doi:

Substances chimiques

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene 0
Boron Compounds 0
Enzyme Inhibitors 0
1-Alkyl-2-acetylglycerophosphocholine Esterase EC 3.1.1.47
Cysteine K848JZ4886

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

7052-7065

Auteurs

Fubao Huang (F)

State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Hangchen Hu (H)

CAS Key Laboratory of Receptor Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, Beijing 100049, China.

Kai Wang (K)

State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Chengyuan Peng (C)

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Wenwei Xu (W)

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Yu Zhang (Y)

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Jing Gao (J)

CAS Key Laboratory of Receptor Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Yishen Liu (Y)

Nanchang University, Nanchang 330031, China.

Hu Zhou (H)

CAS Key Laboratory of Receptor Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
ORCID: 0000-0001-7006-4737

Ruimin Huang (R)

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Minjun Li (M)

Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201203, China.

Jianhua Shen (J)

State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
ORCID: 0000-0002-9273-3409

Yechun Xu (Y)

CAS Key Laboratory of Receptor Research, Chinese Academy of Sciences, Shanghai 201203, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
ORCID: 0000-0002-1581-6155

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Carboxylic ester hydrolases › Phospholipases A › Phospholipases A2 › 1-Alkyl-2-acetylglycerophosphocholine esterase › Identification of Highly Selective...
questionsmedicales.fr › Composés chimiques organiques › Composés du bore › Identification of Highly Selective...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Cystéine › Identification of Highly Selective...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Identification of Highly Selective...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Identification of Highly Selective...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Identification of Highly Selective...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of Highly Selective...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Identification of Highly Selective...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Identification of Highly Selective...