APILIMOD

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

Off-White Solid

Apilimod is a small-molecule that selectively suppresses synthesis of IL-12 and IL-23. Apilimod reduces dendritic cell infiltration in psoriasis.

Wada et al. (2007), Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL23 inhibitor; Blood 109 1156 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 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 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