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Focal segmental glomerulosclerosis (FSGS) is a scarring process associated with chronic low‐grade inflammation ascribed to toll‐like receptor (TLR) activation and monocyte migration. We developed synthetic, small‐molecule lecinoxoids, VB‐201 and VB‐703, that differentially inhibit TLR‐2‐ and TLR‐4‐mediated activation and monocyte migration. The efficacy of anti‐inflammatory lecinoxoid treatment on FSGS development was explored using a 5/6 nephrectomy rat model.
AbstractBinding of chemokines to their cognate receptors on monocytes instigates a cascade of events that directs these cells to migrate to sites of inflammation and cancerous tissues. Although targeting of selected chemokine receptors on monocytes exhibited preclinical efficacy, attempts to translate these studies to the clinic have failed thus far, possibly due to redundancy of the target receptor.
Identification of Motile Sperm Domain–Containing Protein 2 as Regulator of Human Monocyte Migration Itzhak Mendel, Niva Yacov, Yaniv Salem, Oshrat Propheta-Meiran, Eti Ishai, Eyal Breitbart The Journal of Immunology January 30, 2017, 1601662; DOI: 10.4049/jimmunol.1601662
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