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Overview
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Background
YM201636 is a potent, selective and cell-permeable inhibitor of mammalian class III phosphatidylinositol phosphate kinase PIKfyve with IC50 value of 33nM [1].The pyridofuropyrimidine compound, YM201636, is a small-molecule inhibitor of PIKfyve. In the in vitro assay, it inhibits PIKfyve with IC50 value of 33nM and shows no inhibition of yeast orthologue of PIKfyve. It inhibits PtdIns3P p110α and type Iα PtdInsP kinase with IC50 values of 3μM and > 2μM, respectively. The type IIγ PtdInsP kinase is found to be insensitive to YM201636. In serum-starved NIH3T3 cells, YM201636 inhibits PtdIns (3, 5) P2 production by 80% at concentration of 800nM. Acute treatment of YM201636 to MEFs, MDCK, MCF10A, COS7 and NIH3T3 cells causes the formation of large vesicular structures. Besides that, YM201636 is also found to reduce the Akt phosphorylation and GLUT4 cell surface translocation through inhibiting the insulin-dependent class I PI 3k activation [1, 2].
[1] Jefferies H B J, Cooke F T, Jat P, et al. A selective PIKfyve inhibitor blocks PtdIns (3, 5) P2 production and disrupts endomembrane transport and retroviral budding. EMBO reports, 2008, 9(2): 164-170.
[2] Ikonomov O C, Sbrissa D, Shisheva A. YM201636, an inhibitor of retroviral budding and PIKfyve-catalyzed PtdIns (3, 5) P2synthesis, halts glucose entry by insulin in adipocytes. Biochemical and biophysical research communications, 2009, 382(3): 566-570.
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