PNU-96391A (known as OSU6162) is a weak dopamine (DA) D(2) receptor antagonist with behavioral stabilizing properties. OSU6162 seem to act as stabilizers not only on dopaminergic, but also on serotonergic brain signaling (partial agonist on 5-HT2A receptor). OSU6162 in a phase II European clinical trial in treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. One of the isomer of OSU 6162, has promise for treating Parkinson's disease, Huntington's disease and schizophrenia, but both enantiomers of OSU 6162 had dual effects on behavior, stimulating locomotor activity in 'low activity' animals and inhibiting locomotor activity in 'high activity' animals.

GSK-1482160 is being evaluated for treatment of inflammatory pain (such as arthritis). This compound acts on P2X7 receptors, expressed by cells of innate and adaptive immunity. P2X7 receptors are involved in the production of pro-inflammatory cytokines that are thought to be an important mediator of inflammation. By blocking P2X7 receptors, less inflammatory chemicals are released, which possibly results in less inflammatory pain. Because of its ability to target P2X7R with high selectivity and to be radiolabelled with 11C, GSK-1482160 was suggested to be a useful biomarker for neuroinflammation via positron emission tomography (PET).

GSK2879552 – is an orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, GSK2879552 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the dimethylated form of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival. On October 2016 GlaxoSmithKline plans a phase I/II trial for Myelodysplastic syndromes (Monotherapy, Combination therapy, Second-line therapy or greater) in USA, Canada and Europe (PO) (NCT02929498).

LY-3009120 is an orally available inhibitor of all members of the serine/threonine protein kinase Raf family, including A-Raf, B-Raf, and C-Raf protein kinases, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor LY3009120 inhibits Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. LY3009120 is being investigated in phase I clinical trial.

Safotibant (previously known as LF22-0542) was developed as an antagonist at bradykinin B1 receptor for the topical treatment of diabetic macular edema. This drug participated in phase II clinical trials in Australia, in Belgium and in the Czech Republic. However, further, development was discontinued.

An orally bioavailable inhibitor of cyclin-dependent kinases (CDKs) and thropomyosin receptor kinase A (TRKA), with potential antineoplastic activity. CDK2/TRKA inhibitor PHA-848125 AC potently inhibits cyclin-dependent kinase 2 (CDK2) and exhibits activity against other CDKs including CDK1 and CDK4, in addition to TRKA. Inhibition of these kinases may result in cell cycle arrest and apoptosis of tumor cells that express these kinases. Milciclib is currently in phase II clinical trials for thymic carcinoma, glioma and liver cancer. The most common adverse events are nausea and asthenia, vomiting, myasthenic syndrome, dehydration, hypophosphatemia, cytolytic hepatitis and plantar fasciitis.

PF-03654746 is a potent, selective antagonist of the human H3 receptor, developed by Pfizer. It was in the clinical trial phase II for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy, Tourette syndrome as well as potential anti-allergy applications and in phase I of clinical trial for the treatment of Schizophrenia and Alzheimer's disease, but these investigations were discontinued.

MK-0767 is a potent hypoglycaemic insulin sensitizer being evaluated by Kyorin with potential as an antidiabetic agent. MK-0767 acts as a dual agonist of the peroxisome proliferator-activated receptors alpha and gamma, induced high-affinity interactions of PPARα and PPARγ with the transcriptional coactivator CBP in vitro. In ob/ob mice, MK-0767 normalized hyperglycemia and hyperinsulinemia with equal or greater potency and efficacy than pioglitazone. Treatment of hamsters with MK-0767 produced substantial reductions in blood cholesterol and triglycerides. In dogs, MK-0767 reduced serum cholesterol levels with a potency more than 10-fold greater than simvastatin. The efficacies of MK-0767 and simvastatin were additive when given together.

Licofelone (ML 3000) is a pyrrolizine derivative originally discovered by Merckle GmbH and developed by EuroAllaince with a unique pharmacological profile, which comprises optimal gastrointestinal tolerability and high analgesic and anti-inflammatory activity. These effects are due to balanced and selective inhibition of both cyclo-oxygenase and 5-lipoxygenase. Inhibition of 5-lipoxygenase may reduce the gastrointestinal toxicity associated with other non steroidal anti-inflammatory drugs, which only inhibit cyclooxygenase. Licofelone also has antipyretic and antiaggregatory properties. Clinical and preclinical trials were also undertaken for osteoarthritis, rheumatoid arthritis, asthma, pain and inflammation. However, development for these indications appear to have been discontinued.