K161

K161 is a small molecule pan-inhibitor of Src homology 2 domain-containing inositol phosphatase 1 (SHIP-1) and its paralog SHIP-2. It is primarily investigated for its potential to treat neurodegenerative conditions, specifically Alzheimer's disease (AD), by modulating microglial function. K161 has been shown to enhance the phagocytic ability of human microglial-like cells (HMC3) toward amyloid-beta (Aβ) plaques and apoptotic neurons. Its mechanism involves increasing mitochondrial activity and enlarging the lysosomal compartment, which improves the metabolic fitness and degradative capacity of microglia. Research suggests that K161 may function independently of the TREM2 signaling pathway, making it a potential therapeutic candidate for cases where TREM2 signaling is impaired or where SHIP-1/2 expression is dysregulated. Additionally, SHIP inhibitors like K161 have shown efficacy in mouse models of obesity and metabolic dysfunction.