Tetraethylenepentamine (TEPA) is a low-molecular-weight linear polyamine exerting metal-chelating properties. TEPA is widely used in industrial applications. The principal hazards that arise in working with TEPA are those associated with similar organic amines; namely, a corrosive action on skin and eyes. TEPA biological activity was attributed to its effect on cellular Cu levels as (a) treatment with TEPA resulted in reduction of cellular Cu, and (b) excess of Cu reversed TEPA's activity and accelerated differentiation. TEPA was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Transplanting a population of CD133+ CB cells which were expanded ex vivo for 21 days using SCF, FLT3, IL-6, TPO and the copper chelator TEPA (StemEx) was feasible. The expanded cells were well tolerated, with no infusion-related adverse events observed.

Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

Oritavancin is an glycopeptide antibiotic with bactericidal activity effective in treating infections caused by Gram-positive organisms. It treats complicated skin and skin structure infections. This drug demonstrates similar activity to vancomycin, but it has stronger activity against Staphylococcus and Enterococcus. The pharmacokinetics and pharmacodynamics of oritavancin appear to be favourable and once-daily dosing is likely. The incidence of multi-drug resistant bacteria is increasing and explorations into additional treatment options are essential. Oritavancin is marketed under the brand name Orbactiv. Orbactiv is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms. Oritavancin has the following mechanism of action: 1) Inhibition of the transglycosylation (polymerisation) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors 2) Inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall 3) Disruption of bacterial membrane integrity, leading to depolarisation, increased permeability and rapid cell death.

Tetraethylenepentamine (TEPA) is a low-molecular-weight linear polyamine exerting metal-chelating properties. TEPA is widely used in industrial applications. The principal hazards that arise in working with TEPA are those associated with similar organic amines; namely, a corrosive action on skin and eyes. TEPA biological activity was attributed to its effect on cellular Cu levels as (a) treatment with TEPA resulted in reduction of cellular Cu, and (b) excess of Cu reversed TEPA's activity and accelerated differentiation. TEPA was shown to attenuate the differentiation of ex vivo cultured hematopoietic cells resulting in preferential expansion of early progenitors. A phase I/II trial was performed to test the feasibility and safety of transplantation of CD133+ cord blood (CB) hematopoietic progenitors cultured in media containing stem cell factor, FLT-3 ligand, interleukin-6, thrombopoietin and TEPA. Transplanting a population of CD133+ CB cells which were expanded ex vivo for 21 days using SCF, FLT3, IL-6, TPO and the copper chelator TEPA (StemEx) was feasible. The expanded cells were well tolerated, with no infusion-related adverse events observed.

Donitriptan hydrochloride (F 11356) was developed by Pierre Fabre as a brain penetrant 5-HT1B/1D agonist. Which inhibits capsaicin-induced external carotid vasodilation and produces selective carotid vasoconstriction in various animal species. In January 2001, donitriptan had completed phase I trials for migraine and was scheduled to enter phase II development, but before development in phase II, this drug was discontinued.

Nadoxolol is a beta-adrenergic blocking agent and an antihypertensive drug.

Tigloidine is a tropane alkaloid and a naturally occurring analog of atropine, found in small quantities in Duboisia myoporoides. Tigloidine has been found to be beneficial in the treatment of Parkinsonism, Huntington’s Chorea and spastic paraplegia. Tigloidine may provide relief in parkinsonian patients by increasing the gamma-efferent activity and reducing alpha motoneurone activity. In preclinical models, Tigloidine failed to reverse sedation and ptosis in rats induced by reserpine and tetrabenazine. In mice, amphetamine response was not significantly affected by Tigloidine or atropine. However, in the cat and dog, it was markedly facilitated by Tigloidine but not by atropine.

Elarofiban is a novel nonpeptide glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist. It inhibits thrombin-induced platelet aggregation in human gel-filtered platelets and platelet aggregation in human platelet-rich plasma (PRP) in response to collagen, arachidonic acid, ADP, and SFLLRN-NH(2). Elarofiban had adequate oral pharmacokinetics in dogs and excellent oral pharmacodynamics. Elarofiban has been in phase II clinical trials for the treatment of myocardial infarction and thrombosis. However, this research has been discontinued.

NeuroSearch was developing brasofensine (or NS 2214), an oral dopamine reuptake inhibitor for the treatment of Parkinson's disease. Brasofensine successfully passed phase II clinical trial in patients with Parkinson's disease, The drug was safe and well tolerated. However, NeuroSearch discontinued the development of the drug because of the cis-anti isomerization of the 2α-methyloxime group of brasofensine in favor of NS 2230.