2. Academic Validation
  3. Nouveau benzo-mimetics of 17R-Resolvin D2 are potent resolution agonists for inflammation

Nouveau benzo-mimetics of 17R-Resolvin D2 are potent resolution agonists for inflammation

  • iScience. 2025 Nov 22;28(12):114201. doi: 10.1016/j.isci.2025.114201.
Charles N Serhan 1,  Nan Chiang 1,  Mélissa Simard 1,  Robert Nshimiyimana 1,  Ana R Rodriguez 2,  Seok Joon Mun 3,  Daniel Irimia 3,  Bernd W Spur 2
Affiliations

Affiliations

  • 1 Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 2 Department of Cell and Molecular Biology, Virtua Health College of Medicine & Life Sciences of Rowan University, Stratford, NJ 08084, USA.
  • 3 Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard School of Medicine, Shriners Children's Boston, Boston, MA 02129, USA.
PMID: 41488352 DOI: 10.1016/j.isci.2025.114201
Abstract

The acute inflammatory response is a highly coordinated protective process governed by a superfamily of mediators termed specialized proresolving mediators. This includes the recently uncovered 17R-Resolvin D2 (17R-RvD2). We report 17R-RvD2 is rapidly metabolized and locally inactivated by human macrophages. An analog was prepared in a stereospecific synthesis. This benzo-17R-RvD2 resists rapid enzymatic inactivation and shared 17R-RvD2's pro-resolving actions enhancing human macrophage efferocytosis (pico-nanomolar). In peritonitis, benzo-17R-RvD2 (1 ng/mouse; 2.7 pmol) limited neutrophil infiltration >70%, reduced tumor necrosis factor alpha (TNF-α), and increased interleukin-1 (IL-1) receptor antagonist. The analog (1 nM) also enhanced >50% Escherichia coli killing by human leukocytes, equi-molar potent to 17R-RvD2. Benzo-17R-RvD2 (5 nM) reduced the area of human neutrophil swarms on zymosan-targeted chips >30%, without reducing potency of neutrophil swarms against live Candida clusters. Benzo-17R-RvD2 activated human-RvD2 receptor, EC50 ∼1.5 nM, comparable to 17R-RvD2. This longer-acting benzo-17R-RvD2 stimulated critical events in resolution of inflammation, providing a manufacturable prototype for potent SPM mimetics.

Keywords

Biological sciences; Immunology; Natural sciences.

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