Identification of Novel GPR55 Modulators Using Cell-Impedance-Based Label-Free Technology

Journal of Medicinal Chemistry
Paula MoralesNadine Jagerovic

Abstract

The orphan G protein-coupled receptor GPR55 has been proposed as a novel receptor of the endocannabinoid system. However, the validity of this categorization is still under debate mainly because of the lack of potent and selective agonists and antagonists of GPR55. Binding assays are not yet available for GPR55 screening, and discrepancies in GPR55 mediated signaling pathways have been reported. In this context, we have designed and synthesized novel GPR55 ligands based on a chromenopyrazole scaffold. Appraisal of GPR55 activity was accomplished using a label-free cell-impedance-based assay in hGPR55-HEK293 cells. The real-time impedance responses provided an integrative assessment of the cellular consequence to GPR55 stimulation taking into account the different possible signaling pathways. Potent GPR55 partial agonists (14b, 18b, 19b, 20b, and 21-24) have been identified; one of them (14b) being selective versus classical cannabinoid receptors. Upon antagonist treatment, chromenopyrazoles 21-24 inhibited lysophosphatidylinositol (LPI) effect. One of these GPR55 antagonists (21) is fully selective versus classic cannabinoid receptors. Compared to LPI, the predicted physicochemical parameters of the new compounds suggest a clea...Continue Reading

References

Sep 27, 1996·Biochemical Pharmacology·S R Childers, S A Deadwyler
Sep 4, 2007·Biochemical and Biophysical Research Communications·Saori OkaTakayuki Sugiura
Sep 19, 2007·British Journal of Pharmacology·R G Pertwee
Sep 19, 2007·British Journal of Pharmacology·E RybergP J Greasley
Feb 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jane E LaucknerKen Mackie
Feb 13, 2008·The Journal of Organic Chemistry·Heeseon AnSeung Bum Park
Sep 2, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christopher M HenstridgeAndrew J Irving
Oct 11, 2008·Journal of Biochemistry·Saori OkaTakayuki Sugiura
Feb 24, 2009·Trends in Pharmacological Sciences·Ruth A Ross
Mar 17, 2009·The Journal of Biological Chemistry·Hong YinYu Alice Chen
Sep 3, 2009·The Journal of Biological Chemistry·Ankur KapurMary E Abood
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lauren S WhyteMichael J Rogers
Feb 9, 2010·British Journal of Pharmacology·Christopher M HenstridgeAndrew J Irving
Feb 20, 2010·Current Medicinal Chemistry·Alessio MoriconiAlessandra Topai
Mar 20, 2010·Pharmacology & Therapeutics·Haleli Sharir, Mary E Abood
Apr 8, 2010·Current Topics in Medicinal Chemistry·Tapio Nevalainen, Andrew J Irving
Jul 6, 2010·Drug Discovery Today·Clay W Scott, Matthew F Peters
Dec 28, 2010·Chemistry and Physics of Lipids·Evangelia KotsikorouPatricia H Reggio
Jan 15, 2011·The Journal of Pharmacology and Experimental Therapeutics·Andrew J BrownSimon J Dowell
Mar 4, 2011·Trends in Pharmacological Sciences·Ruth A Ross
Oct 27, 2011·The Journal of Biological Chemistry·Sharon Anavi-GofferRuth A Ross
Dec 20, 2011·Diabetes·José María Moreno-NavarreteRuben Nogueiras
Jan 31, 2012·Biochimica Et Biophysica Acta·Roberto Piñeiro, Marco Falasca
May 4, 2013·The Journal of Pharmacology and Experimental Therapeutics·Julia KarglAkos Heinemann
May 30, 2013·Prostaglandins & Other Lipid Mediators·Atsushi YamashitaTakayuki Sugiura
Jul 23, 2013·Cancer Management and Research·Dinorah Leyva-Illades, Sharon Demorrow
Oct 22, 2013·European Journal of Medicinal Chemistry·Paula MoralesNadine Jagerovic
Jun 20, 2014·The Journal of Biological Chemistry·Estefanía MorenoCristina Sánchez
Jul 23, 2014·British Journal of Pharmacology·N A BalengaR Franco
Feb 12, 2015·Journal of Medicinal Chemistry·Paula MoralesNadine Jagerovic
May 1, 2015·Frontiers in Pharmacology·Derek M Shore, Patricia H Reggio

❮ Previous
Next ❯

Citations

Feb 16, 2017·Journal of Molecular Endocrinology·Eva TuduríRubén Nogueiras

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Combinatorial Chemistry & High Throughput Screening
Guido J R Zaman
Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology
Haleli SharirMary E Abood
© 2022 Meta ULC. All rights reserved