WRW4 is a selective antagonist of formyl peptide receptor 2 (FPR2, formerly known as FPRL1), which is a synthetic C-terminal amidated hexapeptide, its IC50 value for inhibiting the binding of WKYMVm to FPRL2 is 0.23 μM[1, 2]. WRW4 can inhibit intracellular calcium release and ERK phosphorylation induced by FPR2 agonists (such as WKYMVm, MMK‑1, Aβ42, and F peptide), thereby suppressing downstream responses such as chemotaxis, peroxide production, and Aβ42 internalization[3, 4]. WRW4 can alleviate cognitive decline caused by diabetes in mice[5].
In vitro, pretreatment of organotypic hippocampal cultures (OHCs) with WRW4 (10µM) for 30min reversed the anti-inflammatory effect of MR-39 on Aβ-induced inflammation in OHCs[6].
In vivo, WRW4 (10µg, 0.1mL) reversed the anti-inflammatory effect of WKYMV by intraperitoneal injection in mice with experimental peritonitis[7].
References:
[1] Skovbakke, Sarah L., et al. The role of formyl peptide receptors for immunomodulatory activities of antimicrobial peptides and peptidomimetics. Current pharmaceutical design 24.10 (2018): 1100-1120.
[2] Shin, Eun Ha, et al. Trp-Arg-Trp-Trp-Trp-Trp antagonizes formyl peptide receptor like 2-mediated signaling. Biochemical and biophysical research communications 341.4 (2006): 1317-1322.
[3] Bae, Yoe-Sik, et al. Identification of peptides that antagonize formyl peptide receptor-like 1-mediated signaling.The Journal of Immunology 173.1 (2004): 607-614.
[4] Cattaneo, Fabio, Melania Parisi, and Rosario Ammendola. Distinct signaling cascades elicited by different formyl peptide receptor 2 (FPR2) agonists. International journal of molecular sciences 14.4 (2013): 7193-7230.
[5] Uno, Hiroki, Takahide Itokazu, and Toshihide Yamashita. Formyl peptide receptor 2 antagonist WRW4 ameliorates diabetes-induced cognitive decline in mice.Neuroscience Research (2025): 104932.
[6] Trojan, Ewa, et al. The N-formyl peptide receptor 2 (FPR2) agonist MR-39 improves ex vivo and in vivo amyloid beta (1–42)-induced neuroinflammation in mouse models of Alzheimer’s disease. Molecular neurobiology 58.12 (2021): 6203-6221.
[7] Lice, Izabella, et al. Effects of formyl peptide receptor agonists ac9-12 and WKYMV in in vivo and in vitro acute inflammatory experimental models. Cells 11.2 (2022): 228.
















