**Background**
The human formyl peptide receptor-like 1 (FPRL-1), also known as FPR2, is a G protein-coupled receptor expressed on various immune cells, including neutrophils and monocytes. This receptor plays a critical role in modulating inflammatory responses, chemotaxis, and the production of proinflammatory cytokines. Given its involvement in the activation of phagocytic leukocytes and its potential influence on the central nervous system, FPRL-1 has become a significant target for studying autoimmune diseases, rheumatoid arthritis, and anxiety-related disorders. Understanding the precise activation of this receptor is essential for developing therapeutic interventions for inflammatory and psychiatric conditions. In this context, we will introduce a potent and selective FPRL-1 agonist – MMK1.
**Definition**
MMK1 is a potent and selective human formyl peptide receptor-like 1 (FPRL-1/FPR2) agonist with an EC50 value of <2 nM for FPRL-1 and >10,000 nM for FPR1.
**In Vitro and In Vivo Studies**
According to the MMK1 description, this compound is a peptide with the sequence Leu-Glu-Ser-Ile-Phe-Arg-Ser-Leu-Leu-Phe-Arg-Val-Met. Regarding MMK1 biological activity, the compound acts as a potent chemotactic and calcium-mobilizing agonist that activates phagocytic leukocytes and enhances the Pertussis Toxin-sensitive production of proinflammatory cytokines IL-1b and IL-6 by human monocytes. In vitro studies demonstrated that MMK1 induces calcium mobilization in human FPRL1-transfected HEK 293 (FPRL1/293) cells with an EC50 of 2 nM. Furthermore, MMK1 (1 μM; for 4 h) induces the selective migration of FPR2-expressing RBL-2H3 cells.
In terms of MMK1 in vivo application, the compound has been evaluated for its neurological effects in four-week-old male ddY mice. Administration of MMK1 (10-1000 pmol; ICV; 20 min before the test) demonstrated anxiolytic-like activity, with a significant effect observed at a dose of 100 pmol/mouse. In conclusion, MMK1 is a highly selective FPRL-1 agonist that serves as a valuable tool for researching leukocyte activation and anxiolytic mechanisms.
Keywords
MMK1, 271246-66-3, MMK 1, MMK-1, Formyl Peptide Receptor (FPR), Calcium Channel, Ca2+ channels, Ca channels, human formyl peptide receptor like-1, FPRL-1, FPR2, chemotactic, calcium, phagocytic leukocyte, PT
References
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[3] Yoo Jung Park, et al. A novel antimicrobial peptide acting via formyl peptide receptor 2 shows therapeutic effects against rheumatoid arthritis. Sci Rep. 2018 Oct 2;8(1):14664.
[4] Hui Zhao, et al. Rubimetide, humanin, and MMK1 exert anxiolytic-like activities via the formyl peptide receptor 2 in mice followed by the successive activation of DP1, A2A, and GABAA receptors. Peptides. 2016 Sep;83:16-20.