Background
Apilimod inhibits the kinase PIKfyve which phosphorylates PI(3)P to PI(3,5)P2 with an IC50 = 14 nM. PIKfyve has an important role in endosome formation and related pathways. Apilimod also inhibits Interleukin-12 (IL-12) and Interleukin-23 (IL-23) at 1-2 nM levels in cells. Apilimod has recently been shown to inhibit SARS-Cov2 replication in iPSC-derived pneumocyte-like cells and a primary human lung explant model. Apilimod is orally bioavailable and cell-permeable.
References
1) Y. Wada, et al. “Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor” Blood, (2007) 109(3), 1156-1164 doi: 10.1182/blood-2006-04-019398.
2) S. Gayle, et al. “Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma” (2017) 129 (13): 1768–1778. DOI: 10.1182/blood-2016-09-736892.
3) L. Riva et al. “ Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing” Nature (2020) https://doi.org/10.1038/s41586-020-2577-1
