TLR7 agonist 3 is an imidazoquinoline-class Toll-like receptor 7 (TLR7) agonist. TLR7 agonist 3 can activate the TLR7-MyD88 pathway and subsequently initiate the NF-κB/IRF7 signaling cascade. TLR7 agonist 3 can be used in research on antiviral therapy, tumor immunotherapy combination strategies, vaccine adjuvant development, and anti-parasitic applications[1-4].
In vitro, TLR7 agonist 3 (0.1–10μg/mL) was applied to HEK293 cells stably expressing human Toll-like receptor 7, MD2, and a secreted alkaline phosphatase reporter gene driven by an NF-κB/AP-1 promoter for 12h. TLR7 agonist 3 activated the NF-κB pathway and promoted the release of secreted alkaline phosphatase[5]. TLR7 agonist 3 (4–500μM) was added to HEK293 cells for 2h, followed by stimulation with imiquimod (1μg/mL) for 24h. TLR7 agonist 3 inhibited the release of secreted embryonic alkaline phosphatase and antagonized TLR7-mediated NF-κB pathway activation, with an IC₅₀ of 23μM[6].
References:
[1] Shi C, Xiong Z, Chittepu P, et al. Discovery of Imidazoquinolines with Toll-Like Receptor 7/8 Independent Cytokine Induction. ACS Med Chem Lett. 2012 Jun 14;3(6):501-504.
[2] Xie Y, Chi Y, Tao X, et al. Rabies Virus Regulates Inflammatory Response in BV-2 Cells through Activation of Myd88 and NF-κB Signaling Pathways via TLR7. Int J Mol Sci. 2024 Aug 23;25(17):9144.
[3] Song Y, Fan W, Yao C, et al. Design, synthesis and biological evaluation of quinazoline and pyrrolo[3,2-d]pyrimidine derivatives as TLR7 agonists for antiviral agents. Org Biomol Chem. 2024 Apr 3;22(14):2764-2773.
[4] Antas P, Machado MD, Leite-Pinheiro F, et al. VPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells. Cell Mol Biol Lett. 2026 Jan 24;31(1):24.
[5] Shukla NM, Malladi SS, Mutz CA, et al. Structure-activity relationships in human toll-like receptor 7-active imidazoquinoline analogues. J Med Chem. 2010 Jun 10;53(11):4450-65.
[6] Urban Švajger, Žiga Horvat, Damijan Knez, et al. New antagonists of toll-like receptor 7 discovered through 3D ligand-based virtual screening. Medicinal Chemistry Research. 2015 Jul; 24: 362–371.