PIKFYVE and lymphoma: PAC-1 is the first pro-caspase activator compound developed and was designated as an orphan drug by the Food Drug Administration in 2016.32 Enzastaurin is an inhibitor of the protein kinase C (PKC), which failed the phase III treatment for the treatment of lymphoma.33 YM201636, is a PIKfyve (phosphatidylinositol phosphate kinase PIP5KIII) inhibitor, a kinase implicated in PtdIns(3,5)P2 biosynthesis that regulates a number of intracellular membrane trafficking pathways.