ABT-510 is an anti-angiogenesis compound that was under development by Abbott for the treatment of solid tumours, lymphoma and melanoma. It is a synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8).

LANEPITANT is a selective nonpeptide antagonist for the neurokinin-1 receptor. It inhibits neurogenic dural inflammation. LANEPITANT was under development as a potential analgesic drug for the treatment of migraine, arthritis and diabetic neuropathy. However, it failed to show sufficient efficacy to support further development.

Anatibant was a selective small-molecule antagonist of the bradykinin B2 receptor that was undergoing clinical development with Xytis and Fournier for the treatment of brain injuries. Anatibant reduces brain oedema in animal TBI models. Noserious toxicity was found in Phase 1 clinical trials. Following subcutaneous administration of clinically relevant doses, there were no systemic effects but there was pain, inflammation and nodule formation at the injection site. Anatibant inhibits the binding of BK to the B2 receptor. After subcutaneous injection Anatibant is bio-available and crosses the BBB.

Capeserod is benzodioxanoxadiazolone derivative patented by patented by pharmaceutical company Synthelabo S. A. as a novel 5-hydroxytryptamine4 receptor partial agonist with potent cognition-enhancing properties. In cells expressing the 5-HT4(b) and 5-HT4(e) splice variants, Capeserod acted as a partial agonist, stimulating cAMP prodn. with a maximal effect of 40 to 50% of serotonin. However, in the rat esophagus preparation, Capeserod acted as a 5-HT4 antagonist with a pKb of 8.81. In addition, Capeserod potently improved performance in several tests of learning and memory. In the object recognition task, it improved retention at 24 h when administered i.p. or p.o. (0.001-0.1 mg/kg). This effect was antagonized by the 5-HT4 antagonist SDZ 205,557, itself without effect, demonstrating that the promnesic effects of Capeserod are mediated by 5-HT4 agonism. Capeserod also reversed the cognitive deficits of aged rats in the linear maze task and the scopolamine-induced deficit of mice in the water maze task. Furthermore, the combined administration of an inactive dose of Capeserod with the cholinesterase inhibitor rivastigmine resulted in a significant promnesic effect, suggesting a synergistic interaction. Capeserod was devoid of unwanted cardiovascular, gastrointestinal, or central nervous system effects with doses up to more than 100-fold higher than those active in the cognitive tests. These results characterize Capeserod as a novel promnesic agent acting via 5-HT4 receptors, with an excellent preclinical profile.

N-acetylmannosamine (ManNAc), a hexosamine monosaccharide, is the first committed biological precursor of Neu5Ac. N-acetylmannosamine is being investigated as a potential treatment for GNE myopathy. N-acetylmannosamine has being reported to improve the cognitive function in aged animals. It has potential therapeutic application for cognitive dysfunction. N-acetylmannosamine is under investigation for GNE myopathy.

BMS-582949 acts as a dual action kinase inhibitor. It inhibits both p38 mitogen-activated protein kinase (p38 MAPK) activity and activation of p38. As a blocking agent for activation of p38 kinase BMS-582949 appeared to be well suited to resist such cellular responses that would drive p38 activation more strongly. BMS-582949 is in Phase II clinical trials for the treatment of rheumatoid arthritis, psoriasis, and atherosclerosis.

Diminazene is an aromatic diamidine derived from Surfen C. Diminazene is used as aceturate salt. Diminazene is highly active against both Trypanosoma and Babesia spp. It is also of value in the treatment of theileriosis due to Theileria annulata. Diminazene has become the most commonly used therapeutic agent for trypanosomiasis in animals. It is said to be effective in canine, ovine and bovine babesiosis and, unlike some drugs, is less susceptible to relapse. It may also possess antibacterial properties. Diminazene binds to trypanosomal kDNA. This binding does not occur by intercalation but via specific interaction with sites rich in adenine-thymine (A-T) base pairs. Diminazene specifically inhibits mitochondrial type II topoisomerase in viable trypanosomes. Thus, inhibition of DNA replication may also occur via this interaction. Diminazene is extensively distributed in the body of treated animals. Residues of the compound may persist for several weeks, principally in the liver and kidneys, and also, to a lesser extent, in the gastrointestinal tract, lungs, muscle, brain and fat.

Sephin1 is a guanabenz derivative that binds to and inhibits a regulatory subunit of the stress-induced protein phosphatase 1 (PPP1R15A), but not the constitutive PPP1R15B, and lacks beta2-adrenergic activity. Phosphorylation of eIF2α, α subunit of eukaryotic translation initiation factor 2, reduces protein synthesis and prevents the accumulation of misfolded protein in the endoplasmic reticulum (ER). PPP1R15A recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate eIF2α, so inhibiting PPP1R15A activity prolongs the phosphorylation of eIF2α and aids in its prevention of the accumulation of misfolded protein. In vitro, Sephin1 protected cells from lethal protein misfolding and cytotoxic ER stress. In vivo Sephin1 prevented Charcot-Marie-Tooth 1B and ALS diseases in mice.