Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction

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Single-Cell Analysis Reveals the Role of the Neuropeptide Receptor FPR2 in Monocytes in Kawasaki Disease: A Bioinformatic Study

“…Vasoactive intestinal peptide (VIP) can effectively improve corneal inflammation by influencing FPR2 pathway activation [ 44 ]. FPR2 agonists can help improve the healing process after myocardial infarction, thus providing an innovative option for therapy [ 45 ]. Annexin A1 (ANXA1) is an important mediator that regulates glucocorticoid expression, and FPR2 mediates inflammatory response under ANXA1 regulation [ 46 – 48 ].…”

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

“…The frequent interchange of the term 'ANXA1' with 'annexin 1-(2-26)' (e.g. in article titles), when the shorter peptide was actually studied (Walther et al, 2000), likely account for this anomaly, Peptide Small molecule (Hayhoe et al, 2006) (Garcia et al, 2019;Qin et al, 2013Qin et al, , 2017 Pro-inflammatory: fMLF Peptide (Showell et al, 1976 (Perretti et al, 2002) (Ying et al, 2004) (Galvao et al, 2021) (Wan et al, 2011) (Arnardottir et al, 2016;Fiore et al, 1994;Krishnamoorthy et al, 2010) (Garcia et al, 2019(Garcia et al, , 2021Qin et al, 2013Qin et al, , 2017) (Lee et al, 2009) Pro-inflammatory: SAA CRAMP (LL-37), amyloid beta 42 (Aβ 42 )…”

“…Patents for urea derivatives serving as FPR2 modulators are largely claimed by Allergan, Inc, USA. These compounds were identified based on Ca 2+ mobilisation assay using FLIPR for prevention of heart failure in mice (Asahina et al, 2020;Garcia et al, 2021). This molecule has advanced to three Phase I clinical trials (trial identifier: NCT04301310, NCT04464577, NCT03335553).…”

“…More recently, Bristol‐Myers Squibb developed a series of piperidiones containing a 4‐phenylpyrrolidinone motif as orally active FPR2 agonists. In collaboration with Kyorin, BMS‐986235/LAR‐1219 demonstrated efficacy for prevention of heart failure in mice (Asahina et al, 2020; Garcia et al, 2021). This molecule has advanced to three Phase I clinical trials (trial identifier: NCT04301310, NCT04464577, NCT03335553).…”

“…In human myocardium, there is evidence suggesting FPR2 may traverse from its physiological sarcolemmal location into the cytoplasm in ischaemic heart disease, based on differences in FPR2 localization in donor left ventricle (LV) samples from ischaemic versus healthy myocardium (Tourki, Kain, Pullen, et al, 2020), albeit there are also marked differences in ethnicity and concomitant medication between the two cohorts. FPR2 agonists such as ANXA1 (Tourki, Kain, Pullen, et al, 2020), Ac‐ANXA1 (2‐26) (Qin et al, 2019), RvD1 (Kain et al, 2015), BMS‐986235 (Asahina et al, 2020; Garcia et al, 2021) and LXA 4 (Kain et al, 2017) are cardioprotective in experimental models of myocardial infarction. Additionally, the small‐molecule non‐selective FPR1/FPR2 agonist compound 17b has proven highly effective in limiting myocardial ischaemia‐reperfusion injury (Qin et al, 2017).…”