Phosphorylcholine (ChoP) is a small zwitterionic amino alcohol, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is the precursor metabolite of choline in the glycine, serine, and threonine metabolism pathways and in intermediate between choline and cytidine-diphosphate choline in the glycerophospholipid metabolism pathway. Phosphorylcholine is an interesting compound from an immunologic point of view, being an immunodominant determinant of pneumococcal teichoic acids and also a major prerequisite for proinflammatory effects of PAF and PAF-like lipids where PC is a common denominator. PC is also a component of some bacteria, apoptotic cells, and OxLDL, which, if exposed, is immunogenic. PC has several properties that could in principle both promote and protect against disease, depending on the pathogen and type of inflammatory reaction. In the field of interventional cardiology, phosphorylcholine is used as a synthetic polymer-based coating, applied to drug-eluting stents, to prevent the occurrence of coronary artery restenosis. To date, more than 120,000 Phosphorylcholine-coated stents have been implanted in patients with no apparent deleterious effect in the long term compared to bare metal stent technologies

Banoxantrone (formally known as AQ4N), a bioreductive drug that is irreversibly converted to AQ4, a stable DNA affinic cytotoxic compound. Banoxantrone is activated by haem-containing reductases such as inducible nitric oxide synthase (iNOS). In hypoxic cells, AQ4N is reduced to the topoisomerase II inhibitor AQ4. By inhibition of topoisomerase II within these hypoxic areas, AQ4N has been shown to sensitize tumors to existing chemo- and radiotherapy treatments. Novacea, the company which was responsible for clinical trials for banoxantrone had decided to scale back on its clinical development, including discontinuing the clinical trial in acute lymphoblastic leukemia and delaying the planned clinical trial in B-cell lymphoma. The company decided to continue enrollment in an ongoing Phase 1b/2a clinical trial in patients with glioblastoma multiforme. However, further information about these clinical trials are not available. Some recent experiments have shown that targeting hypoxic tumors with high levels of iNOS with a combination of AQ4N and radiotherapy could be a useful clinical therapeutic strategy.

Nemorubicin, a doxorubicin derivative, is a DNA-intercalator, topoisomerase and RNA synthesis inhibitor that was undergoing development with Nerviano Medical Sciences (Nerviano MS; formerly Pharmacia Italia) for the treatment of solid tumours, specifically, the loco-regional treatment of primary liver tumours (hepatocellular carcinoma). The drug is active on tumors resistant to alkylating agents, topoisomerase II inhibitors and platinum derivatives. It works primarily through topoisomerase I inhibition. Of note, Nemorubicin is active in cells with upregulation of the nucleotide excision repair (NER) pathway, where current therapies fail. Nemorubicin is biotransformed in the liver into cytotoxic metabolites that may further contribute to render this drug highly active against primary liver tumors or liver metastases. Clinical trials were conducted in Europe, US and China with Nemorubicin given at different dose-schedules and by different routes of administration: as single agent by systemic IV route, oral route and by intra-hepatic artery (IHA) infusion alone or in combination with cisplatin.

S-nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol that acts as a NO pool. The level of GSNO is tightly regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme that degrades GSNO. GSNOR inhibitors offer a potentially promising option for the management of pre-eclampsia, a cause of maternal death and of perinatal morbidity. The GSNO treatment of traumatic brain injury improved neurobehavioral functions. GSNO can increase the expression of certain proteins at concentrations present in the normal human airway. GSNO has an important role in regulating respiratory function (breathing) and preventing inflammation in the respiratory tract, that is why this compound participated in phase I clinical trials for patients with asthma. In addition, GSNO was studied in the cystic fibrosis airway. The obtained results have shown that GSNO replacement therapy could be an effective treatment. In addition, GSNO was investigated for patients with chronic obstructive pulmonary disease.

Acolbifene, the active metabolite of EM-800, was identified as a pure antagonist that acts on both activation domains of the ERs. It is in Phase III clinical trials for the prevention of breast cancer and vasomotor symptoms (Hot flush) in postmenopausal women. Most commonly reported adverse events included irregular menses, leg/muscle cramps, diarrhea, and hot flashes. No serious adverse events were reported.

Gisadenafil is a phosphodiesterase V inhibitor in clinical development at Pfizer. It had been in phase II clinical trials for the treatment of Benign prostatic hyperplasia; Chronic obstructive pulmonary disease; Erectile dysfunction; Overactive bladder. Treatment-emergent adverse events were: headache, myalgia, dyspepsia, back pain.

Tecadenoson is a novel selective A1 adenosine receptor agonist that is currently being evaluated for the conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. Adenosine is a naturally occurring compound that stimulates all adenosine receptor subtypes in the body, including the A2 adenosine receptor which lowers blood pressure. In non-clinical trials, tecadenoson selectively stimulated the A1 adenosine receptor in the Atrioventricular node (AV node) and slowed the speed of electrical conduction across the AV node, reducing the number of electrical impulses that reached the ventricle, without affecting blood pressure. Clinical studies to date with intravenous tecadenoson suggest that it may slow the speed of AV nodal conduction by selectively stimulating the A1 adenosine receptor, and may avoid blood pressure lowering by not stimulating the A2 adenosine receptor. Thus, it may be possible to use intravenous tecadenoson to convert patients from PSVT to normal sinus rhythm without lowering blood pressure or causing adverse events related to vasodilation such as flushing, palpitations or a headache.

Thiodiglycol is the organosulfur structurally similar to diethylene glycol used as a solvent in a variety of applications ranging from dyeing textiles to inks in some ballpoint pens. In chemical synthesis, it is used as a building block for protection products, dispersants, fibers, plasticizers, rubber accelerators, pesticides, dyes, and various other organic chemicals. In the manufacture of polymers, it is used as a chain transfer agent. Thiodiglycol is a precursor in the production of Sulfur mustard and it is also considered as a “Schedule 2” compound (dual-use chemicals with low to moderate commercial use and high-risk precursors) within the terms of the Chemical Weapons Convention treaty.

Fialuridine I-124 is an isotope-labeled form of fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU), a thymidine nucleoside analog with activity against various herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. Bacterial or herpes virus thymidine kinase (TK) considered to be a target of FIAU. Fialuridine I-124 is a positron emission tomography/computed tomography (PET/CT) tracer that was developed for imaging of cells transfected with the herpes simplex virus 1 (HSV1) thymidine kinase reporter gene. This enzyme transfers a γ phosphate group fom ATP to the 5’ hydroxyl group of pyrimidine deoxynucleosides. The lipophilic tracer diffuses into the cell and is trapped in the cell with HSV1-TK activity, because the phosphorylated tracer cannot pass the plasma membrane. TK gene of bacteria was sufficiently similar to that of the viral TK of HSV1 and fialuridine I-124 could also be phosphorylated by the endogenous bacterial TK. Once phosphorylated by TK, fialuridine I-124 becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT).

Piclamilast (RP 73401), is a selective PDE4 inhibitor. It is comparable to other PDE4 inhibitors for its anti-inflammatory effects. It has been investigated for its applications to the treatment of conditions such as asthma, dermatitis, rheumatoid arthritis. Emesis is the most commonly cited side effect of piclamilast.