Functional N-Formyl Peptide Receptor 2 (FPR2) Antagonists Based on the Ureidopropanamide Scaffold Have Potential To Protect Against Inflammation-Associated Oxidative Stress.
Madia Letizia Stama,Enza Lacivita,Liliya N. Kirpotina,Mauro Niso,Roberto Perrone,Igor A. Schepetkin,Mark T. Quinn,Marcello Leopoldo +7 more
TLDR
A new series of ureidopropanamide derivatives were designed with the goal of converting functional activity from agonism into antagonism and to develop new FPR2 antagonists, and showed that they decreased the production of reactive oxygen species in mouse microglial N9 cells after stimulation with lipopolysaccharide.Abstract:
Formyl peptide receptor-2 (FPR2) is a G protein-coupled receptor belonging to the N-formyl peptide receptor (FPR) family that plays critical roles in peripheral and brain inflammatory responses. FPR2 has been proposed as a target for the development of drugs that could facilitate the resolution of chronic inflammatory reactions by enhancing endogenous anti-inflammation systems. Starting from the structure of the FPR2 agonists (R)- and (S)-4 and 2, we designed a new series of ureidopropanamide derivatives with the goal of converting functional activity from agonism to antagonism and to develop new FPR2 antagonists. Although none of the compounds behaved as antagonist, some of the compounds were able to induce receptor desensitization, thus functionally behaving as antagonists. Evaluation of these compounds in an in vitro model of neuroinflammation showed that they reduced reactive oxygen species (ROS) production in mouse microglial N9 cells after stimulation with lipopolysaccharide (LPS). These FPR2 ligands may protect cells from damage due to inflammation-associated oxidative stress.read more
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Recent advances in the design and development of formyl peptide receptor 2 (FPR2/ALX) agonists as pro-resolving agents with diverse therapeutic potential.
TL;DR: A comprehensive overview of recent progress made in the development of FPR2/ALX agonists which promote resolution and tissue regeneration can be found in this article, where the focus of the review is to provide a comprehensive overview.
Journal ArticleDOI
Allicin Attenuated Advanced Oxidation Protein Product-Induced Oxidative Stress and Mitochondrial Apoptosis in Human Nucleus Pulposus Cells.
Qian Xiang,Zhangrong Cheng,Juntan Wang,Xiaobo Feng,Wenbin Hua,Rongjin Luo,Bingjin Wang,Zhiwei Liao,Liang Ma,Gaocai Li,Saideng Lu,Kun Wang,Yu Song,Shuai Li,Xinghuo Wu,Cao Yang,Yukun Zhang +16 more
TL;DR: A significant role is disclosed in the oxidative stress-induced apoptosis of NP cells, which could be involved in the primary pathogenesis of IDD, and it is revealed that allicin could be a promising therapeutic approach against AOPP-mediated oxidative stress during IDD progression.
Journal ArticleDOI
Formyl Peptide Receptor 2 Activation Ameliorates Dermal Fibrosis and Inflammation in Bleomycin-Induced Scleroderma
Gyu Tae Park,Yang Woo Kwon,Tae Wook Lee,Seong Gyu Kwon,Hyun-Chang Ko,Moon-Bum Kim,Jae Ho Kim +6 more
TL;DR: In this paper, the authors investigated the effects of Fpr2 activation in the treatment of scleroderma fibrosis and found that intradermal administration of WKYMVm, a G protein-coupled receptor that modulates inflammation and host defense by regulating the activation of inflammatory cells, such as macrophages.
Journal ArticleDOI
Identification and validation of a prognostic signature and combination drug therapy for immunotherapy of head and neck squamous cell carcinoma
TL;DR: In this paper, a prognostic signature composed of 13 immune-related genes (IRGs) was constructed by comprehensively computational analyses of hundreds of head and neck squamous cell carcinoma (HNSC) samples.
Journal ArticleDOI
Synthesis and evaluation of novel cyclopentane urea FPR2 agonists and their potential application in the treatment of cardiovascular inflammation.
Monika Maciuszek,Almudena Ortega-Gomez,Sanne L. Maas,Mauro Perretti,Andy Merritt,Oliver Soehnlein,Timothy M. Chapman +6 more
TL;DR: In this article, homology modelling, molecular docking and pharmacophore studies were deployed to assist the rationalization of the structure-activity relationships of known formyl peptide receptor 2 (FPR2) agonists.
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