PIK001

PIK001 is a preclinical, highly potent and selective small-molecule inhibitor of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), developed as a novel therapeutic strategy for multiple myeloma and other malignancies characterized by dependence on autophagy and lysosomal function.[4][5][7] By blocking PIKfyve, PIK001 disrupts endosomal–lysosomal trafficking and autophagic flux, leading to lysosomal dysfunction, accumulation of autophagic vacuoles, and subsequent myeloma cell death, with strong in vitro and ex vivo anti–multiple myeloma activity and synergy with standard agents such as venetoclax.[1][2][4][7] The compound exhibits low-nanomolar biochemical potency (PIKfyve IC50 around 10 nM), high target selectivity within the kinome, and robust antitumor activity in murine myeloma models, positioning it as a differentiated PIKfyve inhibitor relative to earlier tools such as apilimod.[3][6][9][10]