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Literature DB >> 27190599

Identification of a Potent and Selective GPR4 Antagonist as a Drug Lead for the Treatment of Myocardial Infarction.

Hayato Fukuda¹, Saki Ito¹, Kenji Watari², Chihiro Mogi³, Mitsuhiro Arisawa¹, Fumikazu Okajima³, Hitoshi Kurose², Satoshi Shuto⁴.

Abstract

GPR4, a pH-sensing G protein-coupled receptor, is highly expressed in endothelial cells and may be activated in myocardial infarction due the decreased tissue pH. We are interested in GPR4 antagonists as potential effective pharmacologic tools and/or drug leads for the treatment of myocardial infarction. We investigated the structure-activity relationship of a known GPR4 antagonist 1 as a lead compound to identify 3b as the first potent and selective GPR4 antagonist, whose effectiveness was demonstrated in a mouse myocardial infarction model.

Entities: Disease Gene Species

Keywords: GPR4; dibenzazepine derivatives; myocardial infarction; pH-sensing GPCR

Year: 2016 PMID： 27190599 PMCID： PMC4867472 DOI： 10.1021/acsmedchemlett.6b00014

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

10 in total

Review 1. A contemporary view on endothelial function in heart failure.

Authors: Eduard Shantsila; Benjamin J Wrigley; Andrew D Blann; Paramjit S Gill; Gregory Y H Lip
Journal: Eur J Heart Fail Date: 2012-06-07 Impact factor: 15.534

2. Previously postulated "ligand-independent" signaling of GPR4 is mediated through proton-sensing mechanisms.

Authors: Masayuki Tobo; Hideaki Tomura; Chihiro Mogi; Ju-Qiang Wang; Jin-Peng Liu; Mayumi Komachi; Alatangaole Damirin; Takao Kimura; Naoya Murata; Hitoshi Kurose; Koichi Sato; Fumikazu Okajima
Journal: Cell Signal Date: 2007-03-30 Impact factor: 4.315

Review 3. The ASICs: signaling molecules? Modulators?

Authors: Oleg Krishtal
Journal: Trends Neurosci Date: 2003-09 Impact factor: 13.837

4. Myocardial extracellular K+ and H+ increase and noradrenaline release as possible cause of early arrhythmias following acute coronary artery occlusion in pigs.

Authors: H Hirche; C Franz; L Bös; R Bissig; R Lang; M Schramm
Journal: J Mol Cell Cardiol Date: 1980-06 Impact factor: 5.000

Review 5. Endothelial dysfunction, arterial stiffness, and heart failure.

Authors: Catherine N Marti; Mihai Gheorghiade; Andreas P Kalogeropoulos; Vasiliki V Georgiopoulou; Arshed A Quyyumi; Javed Butler
Journal: J Am Coll Cardiol Date: 2012-09-19 Impact factor: 24.094

Review 6. Current state of clinical translation of cardioprotective agents for acute myocardial infarction.

Authors: Robert A Kloner
Journal: Circ Res Date: 2013-08-02 Impact factor: 17.367

7. Changes of extracellular Na+, K+, Ca2+ and H+ of the ischemic myocardium in pigs.

Authors: R Friedrich; H Hirche; U Kebbel; V Zylka; R Bissig
Journal: Basic Res Cardiol Date: 1981 Jul-Aug Impact factor: 17.165

Review 8. Regulation of inflammation by extracellular acidification and proton-sensing GPCRs.

Authors: Fumikazu Okajima
Journal: Cell Signal Date: 2013-07-31 Impact factor: 4.315

9. Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

Authors: Ayaka Tobo; Masayuki Tobo; Takashi Nakakura; Masashi Ebara; Hideaki Tomura; Chihiro Mogi; Dong-Soon Im; Naoya Murata; Atsushi Kuwabara; Saki Ito; Hayato Fukuda; Mitsuhiro Arisawa; Satoshi Shuto; Michio Nakaya; Hitoshi Kurose; Koichi Sato; Fumikazu Okajima
Journal: PLoS One Date: 2015-06-12 Impact factor: 3.240

10. Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.

Authors: Lixue Dong; Zhigang Li; Nancy R Leffler; Adam S Asch; Jen-Tsan Chi; Li V Yang
Journal: PLoS One Date: 2013-04-16 Impact factor: 3.240

10 in total

17 in total

1. Pharmacological inhibition of GPR4 remediates intestinal inflammation in a mouse colitis model.

Authors: Edward J Sanderlin; Mona Marie; Juraj Velcicky; Pius Loetscher; Li V Yang
Journal: Eur J Pharmacol Date: 2019-03-28 Impact factor: 4.432

2. GPR4 deficiency alleviates intestinal inflammation in a mouse model of acute experimental colitis.

Authors: Edward J Sanderlin; Nancy R Leffler; Kvin Lertpiriyapong; Qi Cai; Heng Hong; Vasudevan Bakthavatchalu; James G Fox; Joani Zary Oswald; Calvin R Justus; Elizabeth A Krewson; Dorcas O'Rourke; Li V Yang
Journal: Biochim Biophys Acta Mol Basis Dis Date: 2016-12-07 Impact factor: 5.187

Identification of a Potent and Selective GPR4 Antagonist as a Drug Lead for the Treatment of Myocardial Infarction.

Review 1. A contemporary view on endothelial function in heart failure.

2. Previously postulated "ligand-independent" signaling of GPR4 is mediated through proton-sensing mechanisms.

Review 3. The ASICs: signaling molecules? Modulators?

4. Myocardial extracellular K+ and H+ increase and noradrenaline release as possible cause of early arrhythmias following acute coronary artery occlusion in pigs.

Review 5. Endothelial dysfunction, arterial stiffness, and heart failure.

Review 6. Current state of clinical translation of cardioprotective agents for acute myocardial infarction.

7. Changes of extracellular Na+, K+, Ca2+ and H+ of the ischemic myocardium in pigs.

Review 8. Regulation of inflammation by extracellular acidification and proton-sensing GPCRs.

9. Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

10. Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.

1. Pharmacological inhibition of GPR4 remediates intestinal inflammation in a mouse colitis model.

2. GPR4 deficiency alleviates intestinal inflammation in a mouse model of acute experimental colitis.

3. pH and proton-sensitive receptors in brain ischemia.

4. Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells.

Review 5. Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth.

Review 6. GPR68: An Emerging Drug Target in Cancer.

Review 7. Roles of G protein-coupled receptors in inflammatory bowel disease.

8. Genome-wide screening identifies novel genes implicated in cellular sensitivity to BRAF^V600E expression.

9. Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis.

10. CNS distribution, signalling properties and central effects of G-protein coupled receptor 4.