PLX5622

PLX5622 is a brain-penetrant inhibitor of the colony stimulating factor 1 receptor (CSF1R; IC₅₀ = 0.016 ?M).¹ It is selective for CSF1R over FMS-related tyrosine kinase 3 (FLT3), Kit, Aurora C, and kinase insert domain receptor (VEGFR2; IC₅₀s = 0.39, 0.86, 1, and 1.1 ?M, respectively) and is greater than 100-fold selective for CSF1R over a panel of 230 kinases.^1,2 PLX5622 (65 mg/kg) reduces the number of Iba-1⁺ cells, a marker of reduced microglia activation, in the dorsal horn of the spinal cord in a mouse model of neuropathic pain induced by partial ligation of the sciatic nerve.² It also decreases macrophage levels of TNF-α and IL-1β and infiltration into the sciatic nerve, as well as alleviates mechanical and cold allodynia in the same model. Dietary administration of PLX5622 (1,200 ppm in chow) decreases the number of hippocampal microglia by 90%, as well as reduces the number and volume of retrosplenial and somatosensory cortical amyloid-β (Aβ) plaques in the 5XFAD transgenic mouse model of Alzheimer's disease.¹

1.Spangenberg, E., Severson, P.L., Hohsfield, L.A., et al.Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease modelNat. Commun.10(1)3758(2019) 2.Lee, S., Shi, X.Q., Fan, A., et al.Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic painMol. Pain14(2018)