Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratoses. Imiquimod can also be used to treat certain types of skin cancer called superficial basal cell carcinoma. Imiquimod is particularly useful on areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs. Imiquimod's mechanism of action is via stimulation of innate and acquired immune responses, which ultimately leads to inflammatory cell infiltration within the field of drug application followed by apoptosis of diseased tissue. Imiquimod does not have direct antiviral activity. Studies of mice show that imiquimod may induce cytokines, including interferon-alpha (IFNA) as well as several IFNA genes (IFNA1, IFNA2, IFNA5, IFNA6, and IFNA8) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha genes. In the treatment of basal cell carcinoma, Imiquimod appears to act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. In treating basal cell carcinoma it may increase the infiltration of lymphocytes, dendritic cells, and macrophages into the tumor lesion. Imiquimod is used for the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults. Also indicated for the treatment of external genital and perianal warts/condyloma acuminata in individuals 12 years old and above.

Hydroxychloroquine possesses antimalarial properties and also exerts a beneficial effect in lupus erythematosus (chronic discoid or systemic) and acute or chronic rheumatoid arthritis. Although the exact mechanism of action is unknown, it may be based on ability of hydroxychloroquine to bind to and alter DNA. Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte. This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite. Its ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection. As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown. Hydroxychloroquine is used for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis.

Loxoribine [RWJ 217C7] is an immunostimulant which was developed by Johnson and Johnson. It is a selective agonist for TLR7 (Toll-like receptor 7), which possesses antitumor and antiviral properties and was investigated in a rat model of endometriosis and in addition, in phase I of a clinical trial for patients with advanced cancer.

CPG-52364 is a potent antagonist of toll-like receptors TLR7, TLR8, TLR9. The drug was developed by Coley Pharmaceutical Group (later acquired by Pfizer) for the treatment of immune diseases and reached phase I of clinical trials presumably for systemic lupus erythematosus. However, the development of CPG-52364 was terminated by unknown reason.

Vesatolimod, also known as GS-9620, is being developed in clinical studies for the treatment of chronic hepatitis B viral (HBV) infection, with the goal of inducing a liver-targeted antiviral effect without inducing the adverse effects associated with current systemic interferon-α (IFN-α) therapies. It is demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral doses. GS-9620 is a potent and oral agonist of Toll-like receptor-7, a pattern-recognition receptor whose activation results in innate and adaptive immune stimulation

Resiquimod is an imidazoquinolinamine 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. Resiquimod is used as a topical gel[1] in the treatment of skin lesions[2] such as those caused by the herpes simplex virus[3][4] and cutaneous T cell lymphoma. Due to its immunostimulatory activity, this agent may potentially be used as a vaccine adjuvant.

6-amino-2-(butylamino)-9-((6-(2-(dimethylamino)ethoxy)pyridin-3-yl)methyl)-7,9-dihydro-8H-purin-8-one (DSR-6434) is a small molecule toll-like receptor (TLR)-7 agonist, which didn’t have direct antitumor activity, but enhanced efficacy of ionizing radiation therapy in a model of colorectal carcinoma.

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.

Bropirimine, an immunostimulating agent, and toll-like receptor (TLR7) agonist, with anti-cancer and antiviral properties. Bropirimine may be used in experimental autoimmune encephalomyelitis (EAE) and bladder cancer research. Bropirimine is an immunostimulating agent. The compound induces production of α and β interferons and enhances NK cell function. Bropirimine has antiproliferative effects in cancer cell lines and tumor growth in in vivo models.

Hydroxychloroquine possesses antimalarial properties and also exerts a beneficial effect in lupus erythematosus (chronic discoid or systemic) and acute or chronic rheumatoid arthritis. Although the exact mechanism of action is unknown, it may be based on ability of hydroxychloroquine to bind to and alter DNA. Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte. This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite. Its ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection. As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown. Hydroxychloroquine is used for the suppressive treatment and treatment of acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. It is also indicated for the treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis.