PLX5622

Highly selective (>20 fold over KIT and FLT3, >60 fold over 200 other kinases) and brain-penetrant inhibitor of colony-stimulating factor 1 receptor (CSF1R; IC50 = 16 nM) .1 It prevented plaque formation in 5xFAD1 and 3xTg2 mouse models of Alzheimer’s disease via elimination of microglia in a CSF1R-dependent manner. PLX5622 showed efficacy in a mouse neuropathic pain model via reduction of CD86+ macrophages resulting in reduced expression of pro-inflammatory cytokines.3 It also was able to ameliorate peripheral neuropathy in aging mice.4 PLX5622 displayed neuroprotective effects during the chronic phase of a traumatic brain injury mouse model.5 PLX5622 has also been shown to affect myeloid and lymphoid compartments, indicating that its affects are not limited to microglia and include peripheral immune cells.6