Chiral Me-2-arachidonoyl Glycerols: The First Potent Endocannabinoid Glyceride Templates with Stability to COX-2.

Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
13 Jun 2024
Historique:
received: 18 04 2024
revised: 16 05 2024
accepted: 21 05 2024
pmc-release: 13 06 2025
medline: 19 6 2024
pubmed: 19 6 2024
entrez: 19 6 2024
Statut: epublish

Résumé

2-Arachidonoyl glycerol (2-AG) is the principal endogenously produced ligand for the cannabinoid CB1 and CB2 receptors (CBRs). The lack of potent and efficacious 2-AG ligands with resistance against metabolizing enzymes represents a significant void in the armamentarium of research tools available for studying eCB system molecular constituents and their function. Herein we report the first endocannabinoid glyceride templates with remarkably high potency and efficacy at CBRs. Two of our lead chiral 2-AG analogs, namely, (13

Identifiants

DOI: 10.1021/acsmedchemlett.4c00175 PMID: 38894922 PMC: PMC11181503
pubmed: 38894922
doi: 10.1021/acsmedchemlett.4c00175
pmc: PMC11181503
doi:

Types de publication

Journal Article

Langues

eng

Pagination

965-971

Informations de copyright

© 2024 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Auteurs

Spyros P Nikas (SP)

Center for Drug Discovery and Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.
ORCID: 0000-0001-5052-5292

Lipin Ji (L)

Center for Drug Discovery and Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.

Yingpeng Liu (Y)

Center for Drug Discovery and Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.

Markos-Orestis Georgiadis (MO)

Center for Drug Discovery and Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.

Amey Dopeshwarkar (A)

Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana 47405, United States.

Alex Straiker (A)

Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana 47405, United States.

Shalley Kudalkar (S)

Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
ORCID: 0000-0001-9377-335X

Anastasiia V Sadybekov (AV)

Department of Quantitative and Computational Biology, and Department of Chemistry, Bridge Institute, Center for New Technologies in Drug Discovery and Development, University of Southern California, Los Angeles, California 90089, United States.
ORCID: 0000-0003-3925-983X

Michaela Dvorakova (M)

Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana 47405, United States.

Vsevolod Katritch (V)

Department of Quantitative and Computational Biology, and Department of Chemistry, Bridge Institute, Center for New Technologies in Drug Discovery and Development, University of Southern California, Los Angeles, California 90089, United States.
ORCID: 0000-0003-3883-4505

Ken Mackie (K)

Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana 47405, United States.

Lawrence Marnett (L)

Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
ORCID: 0000-0002-7834-6285

Alexandros Makriyannis (A)

Center for Drug Discovery and Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.
Center for Drug Discovery and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
ORCID: 0000-0003-3272-3687

Classifications MeSH