2-Iminobiotin (2-IB) is a cyclic guanidino analog of biotin (Vitamin B7) and combined neuronal and inducible (but not endothelial) nitric oxide synthase inhibitor that has been demonstrated to improve neuroprotection in animal models of hypoxic-ischemic Brain Injury. While the exact mechanism of action has yet to be defined, 2-Iminobiotin potentially protects against hypoxic-ischemic brain damage by preventing nitric oxide or peroxynitrite-induced mitochondrial damage. In preclinical models, 2-Iminobiotin provides gender-specific neuroprotection against hypoxia-ischemia in neonatal rats by a NO-independent mechanism.

BTZ-043 efficiently inhibits Mtb cell wall synthesis by blocking the decaprenyl- phosphoribose-2′-epimerase (DprE1), necessary for the synthesis of D-Arabinofuranose, a component of arabinogalactan and arabinomannan. Due to this mechanism it is highly selective for Mycobacteria species and does not affect the gut flora. BTZ-043 binds covalently to the enzyme and blocks it irreversibly. BTZ-043 is active against all tested Mtb strains including clinical isolated from MDR and XDR patients. The in vitro MIC ranges between ~0.1 - 80 ng/ml for fast growers, and from 1 - 30 ng/ml for members of the M. tuberculosis complex. In vivo BTZ-043 shows superior activity to INH in mouse models, most prominent after 2 months and thereafter. Synergistic effects with Rifampicin were detected in vitro as well as in vivo. In preclinical toxicology (GLP) studies, BTZ-043 showed a low toxicologic potential, it was well tolerated up to 180 mg/kg in rats. BTZ-043 showed no interaction with the CYP450 enzymes or the hERG channel. Genotoxicity and mutagenicity studies were negative. In vitro metabolism studies implicate an acceptable stability in the human organism with only one main metabolite. Protocols for GMP production in industrial scale are available and high purity of the substance can be achieved easily. Currently the final tolerability studies in two animal models are completed and studies in mice are conducted to better describe the pharmacodynamic drivers.

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.