Apilimod | IL-12 and 23/PIKfyve inhibitor

Apilimod (541550-19-0) is a potent (IC₅₀ = 10 nM IFN-g/LPS-stimulated human PMBC’s; IC₅₀ = 1 nM in IFN-g/SAC-stimulated human PMBC’s) IL-12/IL-23 inhibitor downregulating both at the transcriptional level.  Suppresses Th1 but not Th2 immune response.¹  Inhibition was also observed in human monocytes, monocyte-derived dendritic cells, and THP-1 cells.  Apilimod’s mechanism of action is mediation of TLR signaling via inhibition of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve; IC₅₀ = 14 nM).²  It displayed selective cytotoxic activity in B-cell non-Hodgkin lymphoma compared with normal cells.³  Apilimod prevented infection of VSV-ZEBOV and VSV-SARS-CoV-2 (IC₅₀ = 50 nM) as well as SARS-CoV-2 strain 2019-nCoVB/USA-1WA/2020.⁴

References:

1. Wada et al. (2007), Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL23 inhibitor; Blood 109 1156
2. Cai et al. (2013), PIKfyve, a class III PI-kinase, is the target of the small molecule IL12/23 inhibitor apilimod and a new player in toll-like receptor signaling; Chem. Biol., 20 912
3. Gayle et al. (2016), Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma; Blood, 129 1768
4. Kang et al. (2020), Inhibition of PIKfyve kinase prevents infection by Zaire ebola virus and SARS-CoV-2; Proc. Natl. Acad. Sci. USA 117 20803