NMS-P937 is a selective PLK1 inhibitor. It was developed by Nerviano Medical Sciences and tested in phase I clinical trials.

Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. Basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy. Basimglurant is being under development by Roche for the treatment of treatment-resistant depression (as an adjunct). It is in phase II clinical trials for this indication.

Tanzisertib (CC-930) is a potent and selective inhibitor of JNK1/JNK2/JNK3 with IC50 values of 61 nM, 7 nM and 6 nM respectively. Tanzisertib had been in phase II clinical trials for the treatment of idiopathic pulmonary fibrosis and discoid lupus erythematosus. But this research was discontinued in 2012. In 2011, the compound was granted orphan drug designation in the U.S. and the E.U. for the treatment of idiopathic pulmonary fibrosis. The compound was co-developed by Celgene and Ligand.

Manitimus (FK778) is a synthetic malononitrilamide (MNA) that has been demonstrated to have both both immunosuppressive and anti-proliferative activities. The MNAs inhibit both T-cell and B-cell function by blocking de novo pyrimidine synthesis, through blockade of the pivotal mitochondrial enzyme dihyroorotic acid dehydrogenase, and the inhibition of tyrosine kinase activity. It directly reduced endothelial adhesion molecule up-regulation, inhibited lymphocyte activation, and attenuated lymphocyte-endothelium interactions, critical early steps in graft rejection. Manitimus has been demonstrated to prevent acute allograft rejection in multiple experimental transplant models in rodents, dogs and primates and to be effective in the rat model of chronic renal allograft rejection. It was in clinical studies for the treatment of transplant rejection. Manitimus development has been discontinued.

HU-308 ([(1R,2R,5R)-2-[2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl]-7,7-dimethyl-4-bicyclo[3.1.1]hept-3-enyl]methanol) is a potent, selective agonist for the CB2 receptor. The synthesis and characterization took place in the laboratory of Prof. Mechoulam at the Hebrew University of Jerusalem in the late 1990s. It has analgesic effects, promotes proliferation of neural stem cells,[3] and protects both liver and blood vessel tissues against oxidative stress via inhibition of TNF-α. In vivo, HU-308 has hypotensive, analgesic, and anti-inflammatory activities in mice that can be reversed by the CB2 receptor antagonist SR 144528 but not the CB1 receptor antagonist rimonabant. Pretreatment of mice with HU-308 decreases the I/R-induced tissue damage, inflammatory cell infiltration, tissue, and serum TNF-α, MIP-1, and MIP-2 levels, tissue lipid peroxidation, and apoptosis. HU-308 increases proliferation of HT29 colon cancer cells and growth of tumors in an HT29 mouse xenograft model. The physiological and toxicological properties of this compound have not been evaluated in humans.

JNJ-872 is an inhibitor of influenza virus replication that offers a potential for the treatment of pandemic and seasonal influenza.

Rimeporide (EMD-87580) is an Na/H-exchanger-1 (NHE-1) inhibitor and was initially developed for heart failure. This compound reduces the development of both necrosis and hypertrophy, and it was shown to prevent early death in hereditary cardiomyopathy. Rimeporide regulates sodium, pH, calcium overload, reduces inflammation in several muscles, and decreases skeletal, diaphragm and cardiac fibrosis, and muscle cell degeneration. It was therefore further developed as a drug for treatment in Duchenne muscular dystrophy and other muscular dystrophies. Rimeporide is expected to act as a muscle-sparing agent. A phase I study has been completed in 2018.

Pridopidine is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. As a dopamine stabilizer, pridopidine is thought to reduce the effects of dopamine when there’s too much and increase its effects when there’s too little. Pridopidine, therefore, plays two opposing roles in the brain, which stabilize dopamine levels. In this way, pridopidine is thought to help the brain reestablish a normal balance of neurotransmitters, and thus regain control over motion. Pridopidine intended to treat Huntington’s disease movement symptoms. Pridopidine was well tolerated and had an adverse event profile similar to a placebo.