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.

Trazitiline is an antihistaminic agent.

Vercirnon (GSK-1605786, CCX-282, nTraficet-EN) is a selective, and potent antagonist of human CCR9. Vercirnon binds to the intracellular side of the receptor, exerting allosteric antagonism and preventing G-protein coupling. CCR9 is a tissue-specific lymphocyte trafficking molecule that selectively attracts both B- and T-cells to the small gut. Inhibition of CCR9 by GSK-1605786 may inhibit B- and T-cell entry to the small gut and ameliorate inflammation while leaving immune function at other anatomical sites unaffected. Vercirnon is an orally bioavailable, anti-inflammatory agent that is being developed by ChemoCentryx for treatment of inflammatory bowel disease with an initial focus in Crohn's disease. A pivotal phase III programme of vercirnon was initiated in patients with moderate-to-severe Crohn's disease, however, the programme was suspended when the first pivotal trial failed to meet its primary endpoint. Phase II trials for ulcerative colitis and celiac disease were conducted, however investigations for ulcerative colitis were suspended while no further development has been reported for celiac disease.

FLEZELASTINE, a phthalazinone derivative, an anti-asthmatic/anti-allergic agent. It exhibits inhibition of histamine release and 5-lipoxygenase, calcium antagonistic properties and antagonism at the histamine H1 receptor. FLEZELASTINE is a racemate consisting of (+)- and (-)-enantiomers. Both enantiomers contribute to the pharmacodynamic efficacy of racemic flezelastine.

Thymotrinan (also known as RGH-0205) is a protected synthetic tripeptide patented by Hungarian multinational pharmaceutical and biotechnology company Gedeon Richter Plc. (Richter, Gedeon, Vegyeszeti Gyar Rt) as an immunomodulating agent. Thymotrinan is the shortest thymopoietin fragment, that induces differentiation of CD90 cytotoxic T cell in the thymus. In preclinical models Thymotrinan is shown to exert similar immunomodulatory activities to thymopoietin affecting both humoral and cellular responses. In chronic 28-days i.v. toxicity studies in dogs no adverse reaction has been found. The low toxicity of Thymotrinan is probably attributable to their short half-life.

Tiprotimod is a new synthetic thiazole derivative of cefodizime. It is an immunopotentiator of low molecular weight. The broadest immunological activity was seen for this drug. The drug was able to enhance the delayed type hypersensitivity-response against sheep erythrocytes (SRBC) and to stimulate the humoral immune response against Tetanus toxoid and heat-killed E. coli. In the popliteal lymph node assay, a murine graft-vs-host model, a stimulating effect of the substance was observed when it was administered at the same time of the grafts to rats. These results demonstrate that tiprotimod is a potent immunopotentiator for both humoral and cell mediated immune response in experimental animals. The ability of the tiprotimod molecule to enhance the production of ROS by stimulated polymorphonuclear leukocytes and to act agonistically with TNF-alpha or lipopolysaccharide is abrogated when tiprotimod is part of the cefodizime molecule.

Ticolubant (also known as SB-209247) is a pyridine derivative patented by SmithKline Beckman Corp. as an anti-inflammatory leukotriene B4 receptor antagonist. Ticolubant displays high affinity for the human neutrophil LTB4 receptor, blocks LTB4-induced Ca2+ mobilization, and demonstrates potent oral and topical antiinflammatory activity in a murine model of dermal inflammation. However, Ticolubant did not show significant oral activity in a murine model of inflammation. Development of Ticolubant was discontinued when administration to beagle dogs for 28 days was associated with non-dose-dependant inflammatory hepatopathy, with minimal hepatocellular necrosis being observed in the more severe cases

Phenamazoline is an antazoline derivative. It is a sympathomimetic agent. It was developed as vasoconstrictor but its carbon analog is a vasodilator.

Orazipone (also known as OR-1384 or OR-1958) was developed by Orion Company as thiol-modulating, anti-inflammatory agent. Orazipone inhibits activation of inflammatory transcription factors nuclear factor-kappa B and signal transducer and activator of transcription 1 and decreases inducible nitric-oxide synthase expression and nitric oxide production in response to inflammatory stimuli. This drug had completed phase I clinical studies in Finland for possible use in inflammatory bowel disease, asthma, and chronic obstructive pulmonary disease. In addition, orazipone was studied for the treatment of Crohn's disease. However, all these studies were discontinued.

Eritoran (E-5564) is a synthetic lipid A analog that has been designed to antagonize the effects of lipopolysaccharide (LPS) and has been found to do this by interacting with Toll-like receptor 4, the cell surface receptor for LPS. Preclinical in vitro and in vivo studies of eritoran tetrasodium indicate it can limit excessive inflammatory mediator release associated with LPS and improve survival in sepsis models. Clinically, eritoran was being investigated for the treatment of severe sepsis, septic shock, and other endotoxin-mediated indications. Eritoran development has been discontinued.