Last update 01 Nov 2024

GPR88

Last update 01 Nov 2024

Basic Info

Synonyms

G protein coupled receptor 88, G protein-coupled receptor 88, G-protein coupled receptor 88

+ [4]

Introduction

Probable G-protein coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function.

Drugs associated with GPR88

GPR88 agonist(Bristol-Myers Squibb)

Target

GPR88

Mechanism

GPR88 agonists

Active Org.

Bristol Myers Squibb Co. [+1]

Originator Org.

Bristol Myers Squibb Co.

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GPR88 agonists(Acadia Pharmaceuticals)

Target

GPR88

Mechanism

GPR88 agonists

Active Org.

ACADIA Pharmaceuticals, Inc.

Originator Org.

ACADIA Pharmaceuticals, Inc.

Active Indication

Alzheimer Disease [+7]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BI-9508

Target

GPR88

Mechanism

GPR88 agonists

Active Org.

Boehringer Ingelheim Pharma GmbH & Co., KG

Originator Org.

Boehringer Ingelheim Pharma GmbH & Co., KG

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GPR88

100 Translational Medicine associated with GPR88

0 Patents (Medical) associated with GPR88

Literatures (Medical) associated with GPR88

08 Aug 2024·bioRxiv : the preprint server for biology

Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models.

Article

Author: Inturi, Nikhil Nageswar ; Tavares-Ferreira, Diana ; Kume, Moeno ; Mohammed, Ayaan ; Mwirigi, Juliet M ; Munro, Gordon ; Sankaranarayanan, Ishwarya ; Price, Theodore J ; Petersen, Kenneth A

Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors. To test this hypothesis, we used paclitaxel treatment as the priming stimulus and translating ribosome affinity purification (TRAP) to measure persistent changes in mRNA translation in Nav1.8+ nociceptors. TRAP sequencing revealed 161 genes with persistently altered mRNA translation in the primed state. We identified Gpr88 as upregulated and Metrn as downregulated. We confirmed a functional role for these genes, wherein a GPR88 agonist causes pain only in primed mice and established hyperalgesic priming is reversed by Meteorin. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming.

11 Jul 2024·Journal of Medicinal Chemistry

Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for In Vivo Mouse Studies

Article

Author: Schlecker, Annette ; Recolet, Mandy ; Faye, Vincent ; Eickmeier, Christian ; Young, Kyle ; Steinberg, Edith ; Hoerer, Stefan ; Frauli, Mélanie ; Fer, Mickael ; Kieffer, Brigitte L. ; Klepp, Julian ; Zinser, Alexander ; Cui, Yunhai ; Lebrun, Louison ; Halter, Célia ; Würstle, Klaus ; Breh-Schlanser, Petra ; Schann, Stephan ; Omrani, Azar ; Hoenke, Christoph ; Hucke, Oliver T. ; Heyer, Marjorie ; Schaeffer, Laurent ; Amalric, Camille ; Mayer, Stanislas ; Montel, Florian ; Baron, Luc ; Ben Hamida, Sami ; Viloria, Mélanie ; Franchet, Christel ; Lotz, Noémie ; Darcq, Emmanuel ; Arban, Roberto ; Joseph, Christophe

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have in vivo pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket. We discovered two new GPR88 agonists: One that reduced morphine-induced locomotor activity in a murine proof-of-concept study, and the atropoisomeric BI-9508, which is a brain penetrant and has improved pharmacokinetic properties and dosing that recommend it for future in vivo studies in rodents. BI-9508 still suffers from high lipophilicity, and research on this series was halted. Because of its utility as a tool compound, we now offer researchers access to BI-9508 and a negative control free of charge via Boehringer Ingelheim's open innovation portal opnMe.com.

01 Jul 2024·British Journal of Pharmacology

Molecular insights into orphan G protein‐coupled receptors relevant to schizophrenia

Review

Author: Stewart, Gregory D ; Lu, Yao ; Hatzipantelis, Cassandra J ; Langmead, Christopher J

AbstractSchizophrenia remains a sizable socio‐economic burden that continues to be treated with therapeutics based on 70‐year old science. All currently approved therapeutics primarily target the dopamine D2 receptor to achieve their efficacy. Whilst dopaminergic dysregulation is a key feature in this disorder, the targeting of dopaminergic machinery has yielded limited efficacy and an appreciable side effect burden. Over the recent decades, numerous drugs that engage non‐dopaminergic G protein‐coupled receptors (GPCRs) have yielded a promise of efficacy without the deleterious side effect profile, yet none have successfully completed clinical studies and progressed to the market. More recently, there has been increased attention around non‐dopaminergic GPCR‐targeting drugs, which demonstrated efficacy in some schizophrenia symptom domains. This provides renewed hope that effective schizophrenia treatment may lie outside of the dopaminergic space. Despite the potential for muscarinic receptor‐ (and other well‐characterised GPCR families) targeting drugs to treat schizophrenia, they are often plagued with complications such as lack of receptor subtype selectivity and peripheral on‐target side effects. Orphan GPCR studies have opened a new avenue of exploration with many demonstrating schizophrenia‐relevant mechanisms and a favourable expression profile, thus offering potential for novel drug development. This review discusses centrally expressed orphan GPCRs: GPR3, GPR6, GPR12, GPR52, GPR85, GPR88 and GPR139 and their relationship to schizophrenia. We review their expression, signalling mechanisms and cellular function, in conjunction with small molecule development and structural insights. We seek to provide a snapshot of the growing evidence and development potential of new classes of schizophrenia therapeutics.LINKED ARTICLESThis article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc

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GPR88

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