TLR7/8 agonist 1 is a toll-like receptor ( TLR7 )/ TLR8 dual-agonistic imidazoquinoline.

TLR7/8 agonist 1 dihydrochloride (TLR7/8 agonist-5d) is a TLR7/8 agonist which shows prominent immunostimulatory activities.

Resiquimod (R848) is an imidazoquinoline amine and Toll-like receptor (TLR) agonist with potential immune response modifying activity. Resiquimod exerts its effect through the TLR signaling pathway by binding to and activating TLR7 and 8 mainly on dendritic cells, macrophages, and B-lymphocytes. This induces the nuclear translocation of the transcription activator NF-kB as well as activation of other transcription factors. This may lead to an increase in mRNA levels and subsequent production of cytokines, especially interferon-alpha (INF-a) and other cytokines, thereby enhancing T-helper 1 (Th1) immune responses. In addition, topical application of resiquimod appears to activate Langerhans' cells, leading to an enhanced activation of T-lymphocytes.

TLR7/8 agonist 4 hydroxy-PEG6-acid, a Drug-Linker Conjugate for ADCs, comprises the TLR7/8 agonist 4 and a hydroxy-PEG6-acid linker, suitable for the synthesis of antibody-drug conjugates (ADCs) [1].

Gardiquimod diTFA, an imidazoquinoline analog, is a TLR7/8 agonist. Gardiquimod diTFA could inhibit HIV-1 infection of macrophages and activated peripheral blood mononuclear cells (PBMCs). Gardiquimod diTFA specifically activates TLR7 when used at concentrations below 10 μM. Gardiquimod diTFA could function as both an immune system modifier and a reverse transcriptase inhibitor as a novel therapeutic agent to block systemic and mucosal transmission of HIV-1.[1] [2].

TLR7/8 agonist 9 (Compound 25a), exhibiting EC50 values of 40 nM and 23 nM for hTLR7 and hTLR8 respectively, demonstrates anti-tumor properties and enhances the efficacy of PD-1/PD-L1 blockade treatments. This compound is utilized in cancer immunotherapy research [1].

TLR7/8 agonist 4 (compound 41) is a potent agonist of TLR7/8 with anti-cancer activity [1].

TLR7/8 agonist 8 (compound 24m) is a potent dual agonist for toll-like receptors 7 and 8 (TLR7/8), exhibiting half-maximal effective concentrations (EC50s) of 27 nM for human TLR7 (hTLR7) and 12 nM for human TLR8 (hTLR8). This compound has been shown to enhance the efficacy of PD-1/PD-L1 inhibitors in antitumor activity [1].

3M-011, a potent dual toll-like receptor TLR7/8 agonist and cytokine inducer, serves as a powerful adjuvant to radiotherapy, eliciting significant local and systemic immune responses. Additionally, it effectively inhibits H3N2 influenza viral replication in the nasal cavity and exhibits strong antitumor activity[1][2][3].

TLR7/8 antagonist 2 (Compound 15) is a highly potent and orally active agonist of TLR7/8, exhibiting IC50 values of 4.9 and 0.6 nM for TLR7 and TLR8, respectively. Its strong affinity for these receptors makes it a promising candidate for the treatment and investigation of autoimmune diseases, including lupus erythematosus, which is associated with inappropriate activation of TLR7 and TLR8. Consequently, TLR7/8 antagonist 2 represents a valuable tool for research in the field of autoimmune diseases [1].

TLR7/8 Antagonist 1 (Compound 16c), an imidazoquinoline derivative, is a potent TLR7/8 agonist with IC50 values of 3.91 and 2.19 μM for TLR7 and TLR8, respectively. rel-O-2050 (TLR-2050) is a key target for drug development in infectious diseases, cancer and autoimmune diseases.

Gardiquimod is a TLR7/8 agonist. When used at concentrations below 10 μM, Gardiquimod specifically activates TLR7. Gardiquimod could inhibit HIV-1 infection of macrophages and activated peripheral blood mononuclear cells.

TLR7/8 agonist 4 hydroxy-PEG6-acid hydrochloride, a Drug-Linker Conjugate for ADC synthesis, is the hydrochloride variant of TLR7/8 agonist 4 hydroxy-PEG6-acid, comprising the TLR7/8 agonist 4 component attached to the hydroxy-PEG6-acid linker [1].

NCI 126224, a toll-like receptor 4 (TLR4) antagonist, demonstrates selective inhibition of nitric oxide (NO) production in RAW 264.7 macrophages, triggered by the TLR4 agonist LPS (IC50 = 0.31 µM), as opposed to minimal effects on NO production induced by agonists for TLR7/8 (R-848), TLR1/2 (Pam3CSK4), and TLR3 (poly(I:C)). Nevertheless, it also effectively inhibits NO production initiated by the TLR2/6 agonist FSL-1 at an IC50 of 0.6 µM in the same cell line. Moreover, NCI 126224 suppresses LPS-induced NF-κB activity in BV-2 microglial cells and reduces LPS-triggered increases in IL-1β and TNF-α levels in RAW 264.7 macrophages with IC50 values of 5.92, 0.42, and 1.54 µM, respectively.

D18 is an immune modulator that acts as a dual agonist for TLR7/8 (with EC50 values of 24 nM for hTLR7 and 10 nM for hTLR8, respectively). It enhances the expression of PD-L1 through epigenetic regulation, thereby increasing the sensitivity of tumors to PD-1/PD-L1 blockade. Additionally, D18 functions as a cytotoxin for ADC synthesis, specifically for the ADC HE-S2 [1].