Background
PIKfyve is an enzyme that preferentially phosphorylates phosphatidylinositol-3-phosphate (PI(3)P) to produce PI(3,5)P2 [1]. YM201636 is a derivative of PI-103, which was developed during a PI3-kinase drug discovery programme; however, this particular compound was found to have low inhibitory activity towards PI3- kinase,  while retaining potent activity against PIKfyve [2].

Activity Against PIKfyve

YM201636 has been reported to inhibit PIKfyve with an IC₅₀ of 33 nM and more than 3 µM for p110a (assayed at 50 µM ATP) [2].

References

1        Ikonomov, O. C., Sbrissa, D., Mlak, K. and Shisheva, A. (2002) Requirement for PIKfyve enzymatic activity in acute and long-term insulin cellular effects.Endocrinol. 143, 4742-4754

2        Jefferies, H. B., Cooke, F. T., Jat, P., Boucheron, C., Koizumi, T., Hayakawa, M., Kaizawa, H., Ohishi, T., Workman, P., Waterfield, M. D. and Parker, P. J. (2008) A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding.EMBO Rep 9, 164-70