Fluoroazomycin Arabinoside F-18 (18F-FAZA) is a radiofluorinated 2-nitroimidazole derivative with hypoxia (low oxygen)-specific tracer activity. 18F-FAZA is reduced under hypoxic conditions, forming highly reactive intermediates. In its reduced form, 18F-FAZA covalently binds to macromolecules, thereby accumulating in hypoxic cells (e.g. malignant tumors) and allowing radioisotopic imaging of these particular cells with positron emission tomography (PET). (18)F-FAZA shows superior biokinetics and is, thus, a promising PET tracer for the visualization of tumor hypoxia. Clinical evaluation of 18F-FAZA is currently ongoing, and early results have been reported for head and neck, lung, prostate, and rectal cancers.

D-Methyldopa is an inactive isomer of methyldopa. It is known, that only L-isomer has the ability to inhibit dopa decarboxylase and possesses the antihypertensive activity in man. Moreover, about twice the dose of the racemate (DL-form of methyldopa) is required for the equal antihypertensive effect.

(R)-Mequitazine or V0162 (10-[(3R)-1-azabicyclo[2.2.2]oct-3-ylmethyl]-10H-phenothiazine) is an anticholinergic enantiomer of mequitazine, an existing oral racemic antihistamine commercialized for over 30 years. (R)-Mequitazine was found to be an antagonist at muscarinic acetylcholine receptors behaving as an inverse agonist. (R)-Mequitazine was investigated in clinical trials for the treatment of chronic obstructive pulmonary disease, asthma and urinary incontinence.

Spiroxamine is a spirodecane derivative patented by German multinational pharmaceutical and life sciences company Bayer A.-G. as agrochemical fungicide. Spiroxamine acts as a sterol biosynthesis inhibitor with systemic activity. This active ingredient provides control of powdery mildew caused by the ascomycetous fungus, Uncinula necator (syn. Erysiphe necator) in grapes. In laboratory animals, the technical grade Spiroxamine was moderate to highly acutely toxic by the oral route and slightly acutely toxic by the dermal and inhalation routes of exposure. Spiroxamine was non-irritating to the eyes but moderately irritating to the skin. Spiroxamine caused an allergic skin reaction. Health effects in animals given repeated doses of Spiroxamine included effects on the liver, lining of the gastrointestinal and urogenital tracts, the eye and body weight. Spiroxamine did not cause cancer in animals and did not damage genetic material.

Cinobufotalin, the bufadienolide isolated from toad venom, has displayed antitumor activities in many in vitro systems. It has been shown that cinobufotalin induced significant apoptosis in cultured human lymphoma U-937 cells. It induced DNA fragmentation, mitochondrial membrane potential decrease, and reactive oxygen species (ROS) production in U-937 cells. Cinobufotalin induces cytotoxic effect in cultured lung cancer cells. Cinobufotalin (1/5 mg/kg, i.p. twice daily, for 7 days) significantly inhibited A549 xenograft growth in mice. Further, same cinobufotalin administration improved mice survival at week five. Cinobufotalin administration didn’t significantly affect mice body weight, indicating the relative safety of this regimen. Thus, cinobufotalin inhibits A549 xenograft growth in vivo and improves mice survival.

TRC-150094 is a synthetic compound that displays the capacity to stimulate energy expenditure. TRC-150094 increases whole body energy expenditure, increases mitochondrial fatty acid oxidation (FAO), and reduces abdominal adiposity in rats fed a high-fat diet. TRC-150094 attenuates the progression of hypertension, insulin resistance, dysglycemia, and atherogenic dyslipidemia, factors reported to signify significant cardiovascular (CV) risk amongst viscerally obese dysglycemic subjects. Moreover, at organ level, TRC150094 reduced steatohepatitis, reduced progression of nephropathy, and preserved cardiac contractile function. Pharmacological profile of TRC-150094 may constitute a promising new class of molecules that may have a potential beneficial therapeutic approach for the treatment of nontraditional CV risk factors and may reduce residual risk in viscerally obese dysglycemic patients. Moreover, the observed metabolic and functional effects on skeletal muscle suggest that TRC-150094 as a therapy may help to facilitate adherence to prescribed exercise, which would remain the mainstay along with diet control in such patients. Simultaneous systemic administration of TRC-150094 to rats receiving an high-fat diet results in a reduction in fat accumulation within the liver and a marked reduction in adipose tissue mass. TRC-150094 is in phase-III clinical trials for the treatment of diabetes mellitus, hypertension and dyslipidaemias (adjunctive treatment) in India.

GET-73 (N-[(4-trifluoromethyl)benzyl]4-methoxybutyramide) is a compound with a structure related to that of gamma-hydroxybutyric acid (GHB), which is used in the treatment of alcohol withdrawal. Like GHB, GET-73 has the capacity to reduce alcohol intake in rats. GET-73 also exerts anxiolytic effects in rats and seemed to improve memory in a water maze test. Although the exact mechanism of GET-73 action is still unknown, it was suggested that an allosteric modulation of metabotropic glutamate receptor 5 (mGlu5 receptor) by GET-73 may represent the mechanism underlying the effects of the compound. GET73 was suggested to have a multifaceted pharmacological profile, importantly including the capacity to reduce alcohol drinking and anxiety-related behaviors. A phase II study was completed in November 2018, in which physical effects and changes in cognitive performance as a result of GET-73 administration were studied in alcohol-dependent individuals.

COH-29 is an antimetabolite drug developed at City of Hope Cancer Center. Compound targets human ribonucleotide reductase, a key enzyme in the deoxyribonucleotide biosynthesis. In preclinical studies, COH-29 induced double-strand breaks in BRCA1-defective breast cancer cells and has been shown to reduce tumor growth in leukemia and ovarian cancer models. In 2015, COH-29 was licensed to a biotech company Novonco. The drug is being evaluated in phase 1 clinical trial for the treatment of patients with solid tumors.

IQP-0528 is an antiretroviral pyrimidinedione derivative with activity against human immunodeficiency virus (HIV) in the nanomolar range. It is a non-nucleoside reverse transcriptase inhibitor that also inhibits HIV entry through an unknown mechanism thought to target a conformational epitope formed prior to the fusion of the viral envelope with the host cellular membrane. IQP-0528 is under clinical development for HIV prevention.