(S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027, GIT-027) is an isoxazole compound that exhibits various immunomodulatory properties. This compound reduced the secretion of IL-1beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappaB and p38 MAP kinase pathways along with up-regulation of ERK pathways. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. Inovio Pharmaceuticals is developing VGX-1027 for the treatment of inflammatory conditions such as rheumatoid arthritis, type 1 diabetes mellitus, uveitis and ulcerative colitis.

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.

PBT-1033, also known as PBT-2, is a neural protective agent potentially for the treatment of Alzheimer's disease and Huntington's Disease. PBT-1033 is a moderate-affinity 8-hydroxyquinoline transition metal-ligand that acts as a synthetic chaperone, re distributing copper, zinc, and iron from locations where they are abundant to subcellular locations where they might be deficient. Delivery of copper and zinc by PBT-1033 into the cytoplasm deactivates the kinase glycogen synthase kinase 3β and the phosphatase calcineurin, both potential targets for Huntington’s disease. In aged wild-type mice, PBT-1033 improves cognitive ability and markers of neuronal plasticity and function. In Alzheimer’s disease mouse models, PBT-1033 inhibits the accumulation of amyloid β, attenuates neuropathological effects of amyloid β, including amyloid-β-induced hyperphosphorylation of tau, and improves cognition. In a 12-week, phase 2a, randomized, double-blind, placebo-controlled trial in 78 individuals with mild Alzheimer’s dementia, PBT-1033 was safe and well tolerated and significantly reduced concentrations of amyloid β42 in CSF.