Vatiquinone is the international non-proprietary name for Edison Pharmaceuticals’ EPI-743, an orally bioavailable small molecule being developed by the company for inherited mitochondrial diseases. EPI-743 is a member of the para-benzoquinone class of drugs. The mechanism of action of EPI-743 involves augmenting the synthesis of glutathione, optimizing metabolic control, enhancing the expression of genetic elements critical for cellular management of oxidative stress, and acting at the mitochondria to regulate electron transport. EPI-743 is a compound being developed by BioElectron (previously known as Edison Pharmaceuticals) to treat Friedreich’s ataxia (FA), a rare, autosomal recessive genetic disorder. The regulation of oxidative stress is disturbed in people with FA. EPI-743 targets NADPH quinone oxidoreductase 1 (NQO1), helping to increase the biosynthesis of glutathione, a compound essential for the control of oxidative stress. The drug does not target any FA-specific biochemical pathways directly, but helps to improve the regulation of cellular energy metabolism in general. Vatiquinone has been investigated for the treatment and prevention of retinopathy, rett syndrome, parkinson's disease, noise-induced hearing loss, and methylmalonic aciduria and homocystinuria, Cblc type. The FDA previously granted orphan drug designation for Edison’s EPI-743 to treat inherited respiratory chain diseases of the mitochondria and Friedreich’s ataxia. The company received orphan drug designation for EPI-743 from the Japanese Ministry of Health, Labour and Welfare and European Medicines Agency Committee on Orphan Products for the treatment of Leigh syndrome.

The labeled 4-IODOPHENYLALANINE I-131 is used for proteomics research. It’s also can be used for the chemoselective modification of proteins.

Rimiducid (AP1903) is a lipid-permeable tacrolimus analogue with homodimerizing activity. Rimiducid homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val). This agent is used to homodimerize the Fv-containing drug-binding domains of genetically engineered proteins such as the iCD40 receptor, Fas intracellular domain or iCaspase 9 resulting in downstream signaling activation during cell therapy. Orphan designation was granted for rimiducid (AP1903) for the treatment of graft-versus-host disease.

Miransertib (ARQ 092) is a selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. Miransertib binds inactive AKT, preventing membrane localization and subsequent AKT activation, and binds active AKT, resulting in direct inhibition. Miransertib participates in Phase 1/2 of clinical trials to treat patients at least 2 years of age with PIK3CA-related Overgrowth Spectrum (PROS) and Proteus syndrome (PS). In addition, the drug is involved in the phase I trial in patients with lymphoma, endometrial cancer, and AKT1 E17K mutations. Recently was shown that miransertib could be an excellent lead compound for the development of new oral drug therapy for visceral and cutaneous leishmaniasis.

GKT137831, a novel pyrazolopyridinedione derivative, a dual inhibitor of NADPH oxidases (NOX) 1 and NOX4, reduces inflammation in the ischemic retina by dampening the pro-inflammatory phenotype of retinal immune cells as well as macroglial Müller cells and neurons. In patients with diabetic kidney disease, GKT137831 demonstrated an excellent safety profile and statistically significant reduction in both liver enzyme and inflammatory marker levels in multiple phase I and phase II clinical studies. GKT137831 may be of significant benefit for patients with systemic sclerosis as studies in experimental models show that the compound may reduce the abnormal growth of connective tissue (fibrosis) and improve survival. GKT137831 was granted Orphan Drug designation for the treatment of systemic sclerosis from the FDA and the EMA. GKT-137831 acts as a Nox4 and Nox1 inhibitor ((Ki 100–150 nM). GKT-137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Also a potent inhibitor of fibrosis and hepatocyte apoptosis.

Verdiperstat (formerly known as AZD 3241) was developed as a selective inhibitor of myeloperoxidase, an enzyme that acts as a key driver of pathological oxidative stress and inflammation in the brain. Verdiperstat was studied in patients with a number of neurodegenerative disorders, including multiple system atrophy and Parkinson's disease. Verdiperstat participated in phase II clinical trials for both diseases. As a result, studies for Parkinson disease were discontinued. In the case of multiple system atrophy, the drug has received the orphan drug status.

Tirasemtiv is a fast skeletal troponin activator and is a candidate amyotrophic lateral sclerosis (AML) therapeutic. It is a small molecule that enhances the signals between motor neurons and neuromuscular junctions. Tirasemtiv increases muscle strength by amplifying the response of muscle when neuromuscular input is diminished secondary to a neuromuscular disease. Tirasemtiv selectively binds to the fast skeletal troponin complex, thus slowing down the rate of calcium release from troponin C and sensitizing muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards as does the force-frequency relationship of a nerve-muscle pair.

Lucerastat inhibits glycolipid biosynthesis. Lucerastat is an orally bioavailable inhibitor of glucosylceramide synthase. Lucerastat is being developed by the biopharmaceutical company Idorsia for the treatment of Fabry disease.

FLORILGLUTAMIC ACID F-18 is a radioactive L-glutamate derivative and a tumor-specific positron emission tomography (PET) tracer. Orphan designation (EU/3/16/1632) was granted by the European Commission to Piramal Imaging GmbH, Germany, for FLORILGLUTAMIC ACID F-18 for the diagnosis of hepatocellular carcinoma. Currently, it is in phase II trial as a PET tracer in early lung cancer in patients with lung nodules.

Pocapavir is a capsid-binding molecule. It is a capsid inhibitor that blocks virus uncoating and viral RNA release into cells, which in turn prevents virus replication. Pocapavir is a potent, selective, anti-enterovirus molecule with in vitro and in vivo activities. Antiviral testing against viruses of the 15 most commonly isolated enterovirus serotypes indicates that pocapavir inhibits 80% of the immunotypes (154 viruses) at a concentration that is within the levels of the molecule achievable in plasma after oral dosing in higher animals. Persistent low viral load after therapy completion may indicate lack of antiviral effect from pocapavir for neonatal enteroviral sepsis treatment. Pocapavir had been in phase II clinical trial for the treatment of poliomyelitis but no recent reports on development were identified.