AJ2-30

AJ2-30 is an inhibitor of the endolysosome transporter solute carrier family 15 member A4 (SLC15A4).¹ It is selective for SLC15A4 over SLC15A3 at 5 µM. AJ2-30 reduces increases in IFN-α levels induced by the toll-like receptor 9 (TLR9) agonist CPG-2216 in primary human plasmacytoid dendritic cells (IC₅₀ = 1.8 µM). It also inhibits NOD2 signaling mediated by the NOD2 ligand muramyl dipeptide (MDP; Item No. 30866) in a reporter assay using A549 cells expressing membrane-localized SLC15A4 (IC₅₀ = 2.6 µM). AJ2-30 reduces increases in IFN-α and IL-6 induced by the TLR9 agonist CPG-2006 or the TLR7 agonist R-837 (imiquimod; Item No. 14956) in peripheral blood mononuclear cells (PBMCs) isolated from patients with systemic lupus erythematosus (SLE). It reduces IFN-α, IFN-β, and IFN-γ production induced by a CPG-2216-DOTAP complex in mice when administered at a dose of 50 mg/kg.

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1. Chiu, T.Y., Lazar, D.C., Wang, W.W., et al. Chemoproteomic development of SLC15A4 inhibitors with anti-inflammatory activity. Nat. Chem. Biol. Online ahead of print, (2024).