SR-57227A is a potent and selective agonist at the 5HT3 receptor, with high selectivity over other serotonin receptor subtypes and good blood-brain barrier penetration. SR-57227A had affinities (IC50) varying between 2.8 and 250 nM for 5-HT3 receptor binding sites in rat cortical membranes and on whole NG 108-15 cells or their membranes in vitro. SR 57227A stimulated the uptake of [14C]guanidinium into NG 108-15 cells in the presence of substance P and contracted the isolated guinea-pig ileum, effects that were antagonized by the 5-H 3 receptor antagonist tropisetron. The agonist effect of SR 57227A was also observed in vivo, as the compound elicited the Bezold-Jarisch reflex in anesthetized rats, an effect that was blocked by tropisetron.

Sazetidine-A (6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol or AMOP-H-OH) is a "silent desensitizer" of neuronal nicotinic acetylcholine receptors (nAChRs), meaning that it desensitizes the receptor without first activating it. Later it was shown that Sazetidine-A is an agonist of native and recombinant alpha4beta2 nAChRs but shows differential efficacy on alpha4beta2 nAChRs subtypes. In animal models it is able to regulate the gain in body weight, alcohol and nicotine dependence. Sazetidine-A exerts analgesic, antidepressant and anxiolytic properties.

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.

PF-03246799 (PF-3246799) is a potent 5-HT2C receptor agonist. PF-3246799 had minimal activation at either the 5-HT2A or 5-HT2B receptors, combined with robust efficacy in a preclinical canine model of SUI and attractive pharmacokinetic and safety properties. It is a candidate for clinical development for the treatment of SUI.

GPR40 agonist with potential therapeutic activity against diabetes.