Gardiquimod, an imidazoquinoline compound, is a specific toll-like receptor 7 (TLR7) agonist. It acts as an immune response modifier and is a potential anticancer and antiviral agent. The core structure of gardiquimod is 1H-imidazo[4,5-c]quinoline like in imiquimod, TLR7 agonist approved by FDA that exerts antiviral and antitumor effects. Like imiquimod, gardiquimod induced the activation of NF-κB in HEK293 cells expressing human or mouse TLR7, however, gardiquimod is 10 times more active than imiquimod. Gardiquimod, markedly activated both porcine TLR7 and TLR8 whereas only human TLR7, but not TLR8. In in-vitro studies gardiquimod exhibited antitumor properties including inhibition of cell proliferation, migration, and apoptosis induction of the human pancreatic adenocarcinoma cell line, suppression of the growth of human HepG2 liver carcinoma xenografts. Gardiquimod inhibited murine B16 melanoma growth and metastasis enhancing the expression of costimulatory molecules and IL-12 by macrophages and bone marrow-derived dendritic cells (DCs). It directly activated NK cells, promoting the maturation of immature DCs. Gardiquimod demonstrated more potent antitumor activity than imiquimod suggesting that it may serve as potent innate and adaptive immune response modifier in tumor therapy or as vaccine adjuvants to potentiate the efficiency of DC-based tumor immunotherapy. Gardiquimod inhibited HIV type 1 infection of human macrophages and activated T cells. Gardiquimod treatment of both activated PBMCs and macrophages induced interferon-alpha (IFN-α) transcription within hours of addition, and sustained IFN-α protein secretion for several days. It inhibited HIV-1 reverse transcriptase, an early step in the life cycle of HIV-1. Thus, functioning as both an immune system modifier and a reverse transcriptase inhibitor, gardiquimod could be developed as a novel therapeutic agent to block systemic and mucosal transmission of HIV-1. Gardiquimod pretreatment provided independent of TNF and dependent on IFNAR neuroprotection before middle cerebral artery occlusion in mice. Reduces infarct volume as well as functional deficits in mice were observed.

Gardiquimod, an imidazoquinoline compound, is a specific toll-like receptor 7 (TLR7) agonist. It acts as an immune response modifier and is a potential anticancer and antiviral agent. The core structure of gardiquimod is 1H-imidazo[4,5-c]quinoline like in imiquimod, TLR7 agonist approved by FDA that exerts antiviral and antitumor effects. Like imiquimod, gardiquimod induced the activation of NF-κB in HEK293 cells expressing human or mouse TLR7, however, gardiquimod is 10 times more active than imiquimod. Gardiquimod, markedly activated both porcine TLR7 and TLR8 whereas only human TLR7, but not TLR8. In in-vitro studies gardiquimod exhibited antitumor properties including inhibition of cell proliferation, migration, and apoptosis induction of the human pancreatic adenocarcinoma cell line, suppression of the growth of human HepG2 liver carcinoma xenografts. Gardiquimod inhibited murine B16 melanoma growth and metastasis enhancing the expression of costimulatory molecules and IL-12 by macrophages and bone marrow-derived dendritic cells (DCs). It directly activated NK cells, promoting the maturation of immature DCs. Gardiquimod demonstrated more potent antitumor activity than imiquimod suggesting that it may serve as potent innate and adaptive immune response modifier in tumor therapy or as vaccine adjuvants to potentiate the efficiency of DC-based tumor immunotherapy. Gardiquimod inhibited HIV type 1 infection of human macrophages and activated T cells. Gardiquimod treatment of both activated PBMCs and macrophages induced interferon-alpha (IFN-α) transcription within hours of addition, and sustained IFN-α protein secretion for several days. It inhibited HIV-1 reverse transcriptase, an early step in the life cycle of HIV-1. Thus, functioning as both an immune system modifier and a reverse transcriptase inhibitor, gardiquimod could be developed as a novel therapeutic agent to block systemic and mucosal transmission of HIV-1. Gardiquimod pretreatment provided independent of TNF and dependent on IFNAR neuroprotection before middle cerebral artery occlusion in mice. Reduces infarct volume as well as functional deficits in mice were observed.