Apilimod

Apilimod is an inhibitor of the class III phosphatidylinositol kinase PIKfyve (IC₅₀ = 14 nM).¹ It is selective for PIKfyve over 10 other lipid kinases and 31 other protein kinases (IC₅₀s = >9.1 µM for all). Apilimod inhibits the production of IL-12p40 induced by IFN-γ and LPS or the TLR7 agonist R-837 (imiquimod; Item No. 14956) in isolated human peripheral blood mononuclear cells (PBMCs; IC₅₀s = 2.4 and 3 nM, respectively) and the production of IL-23 induced by IFN-γ and S. aureus Cowan I (SAC) in isolated human PBMCs (IC₅₀ = 10 nM).^1,2 It prevents infection of Vero E6 cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; EC₅₀ = 23 nM).³ Apilimod reduces cell viability in a panel of B cell non-Hodgkin lymphoma cell lines with a mean IC₅₀ value of 142 nM.⁴ It decreases disease severity in a CD4⁺CD45Rb^high T cell transfer mouse model of inflammatory bowel disease (IBD) when administered at a dose of 10 mg/kg, as well as in a mouse model of experimental autoimmune uveoretinitis induced by the peptide IRBP_1-20 (Item No. 36727).^2,5

WARNING This product is not for human or veterinary use.

1. Cai, X., Xu, Y., Cheung, A.K., et al. PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling. Chem. Biol. 20(7), 912-921 (2013).

2. Wada, Y., Lu, R., Zhou, D., et al. Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood 109(3), 1156-1164 (2007).

3. Riva, L., Yuan, S., Yin, X., et al. Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature 586(7827), 113-119 (2020).

4. Gayle, S., Landrette, S., Beeharry, N., et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood 129(13), 1768-1778 (2017).

5. Keino, H., Watanabe, T., Sato, Y., et al. Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis. Arthritis Res. Ther. 10(5), (2008).