Toll-like receptor 9 and Z-DNA binding protein 1 (TLR9/ZBP1)

IMT504 is the prototype of a novel class of immunomodulatory oligonucleotides (ODNs) characterized by the non-CpG motif PyNTTTTGT. Unlike traditional CpG-containing ODNs that primarily target Toll-like receptor 9 (TLR9), IMT504 exerts its effects through a distinct mechanism that involves both the modulation of TLR9 and the activation of the cytosolic DNA sensor Z-DNA binding protein 1 (ZBP1), also known as DNA-dependent activator of IFN regulatory factors (DAI). This interaction triggers a potent Th1-type immune response, leading to the activation of B cells, plasmacytoid dendritic cells, and natural killer (NK) cells, and the subsequent secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Notably, IMT504 does not induce type I interferon secretion in plasmacytoid dendritic cells and can inhibit CpG-induced IFN-α production, distinguishing it from classic TLR9 agonists. Beyond its application as a vaccine adjuvant for infectious diseases like rabies and hepatitis B, IMT504 has shown significant therapeutic potential in regenerative medicine by promoting the expansion and mobilization of endogenous mesenchymal stem cells (MSCs). This regenerative capacity has been leveraged in preclinical models to treat conditions such as type 1 diabetes, sepsis, and chronic neuropathic pain.

Other names

TLR9ZBP1DAIDLM-1DNA-dependent activator of IFN regulatory factorsPyNTTTTGT receptorNon-CpG oligonucleotide receptor

Agonist of Toll-like receptor 9 and activator of the Z-DNA binding protein 1 (DAI) pathway