Halofuginone is a low molecular weight quinazolinone alkaloid, and a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also effectively suppresses tumor progression and metastasis in mice. Halofuginone is a potent inhibitor of collagen a1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. Also was shown that halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The profound antitumoral effect of halofuginone is attributed to its combined inhibition of tumour-stromal support, vascularization, invasiveness, and cell proliferation. HT-100 (delayed-release halofuginone), currently in clinical phase 1b/2a in five U.S. hospitals, is a small molecule drug candidate taken orally for the treatment of Duchenne muscular dystrophy (DMD) patients primarily through its ability to reduce fibrosis and inflammation and promote muscle fiber regeneration. The medicine candidate has been granted orphan drug designation in the U.S. and the EU — meaning it has been commercially undeveloped due to its limited profitability — and fast-track designation in the U.S. — an FDA process that aims to facilitate the development and patients’ reach to novel therapies for unmet medical needs.

Streptoniazid is a streptomycin derivative patented by Societe des usines chimiques de Rhone-Poulenc as antibiotic effective against tuberculosis.

Anilopam is an opioid analgesic of the benzazepine class. It is an opioid receptor agonist.

Coumazoline is a vasoconstrictor developed as a nasal decongestant by a French corporation Labez. Intravenous administration of the compound to dogs lead to a marked and prolonged drop in the temperature of the gingival mucosa. In rats, coumazoline caused slowing of the dye diffusion on the surface of the skin. The compound did not influence the ciliary motility, as was measured on an isolated guinea pig trachea.

Fosmidomycin (3-(formylhydroxyamino)-propylphosphonic acid mono-sodium salt, 3-(N-formyl-N-hydroxyamino)-propylphosphonic acid mono-sodium salt, FR-31564) is a potent inhibitor of P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR), developed by Albert Schweitzer Hospital for P. falciparum malaria treatment. Fosmidomycin was originally isolated as natural antibiotic from Streptomyces lavendulae. Fosmidomycin is active against a broad range of enterobacteria, but not against Gram-positive organisms or anaerobes. Fosmidomycin was developed as far as an early phase II study for the treatment of urinary tract infections by Fujisawa Pharmaceutical Company (Osaka, Japan) in the early eighties, but these trials have been discontinued. In recent clinical studies, it was shown that fosmidomycin is effective in curing uncomplicated Plasmodium falciparum malaria in humans. The treatment was well tolerated and resulted in a fast parasite and fever clearance. However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy. In drug combination studies, the synergy of fosmidomycin with clindamycin was observed. Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.

Clovoxamine is an antidepressant and anxiolytic drug, acting as a serotonin and norepinephrine reuptake inhibitor. The drug was investigated in the double-blind clinical trials for the treatment of anxiety neurosis, where it was compared with diazepam, and found to have comparable efficacy but higher drop out rate.

Conorphone (TR5109) is an opioid of mixed agonist-antagonist analgesic class. In animal models, conorphone demonstrated an analgesic activity in the same range as morphine, and lack of addiction liability. Conoprphone was evaluated in a clinical trial for postoperative pain in the oral surgery model and in patients with postepisiotomy pain. The 40 mg dose of conorphone resulted in a significant incidence of side effects such as drowsiness, dizziness, nausea, and vomiting.

Hycanthone is a thioxanthene derivative of lucanthone with anti-schistosomal activity and potential antineoplastic activity. It was clinically available for the treatment of human schistosomiasis. Anti-helmintic action relies on its ability to inhibit worm monoamine oxidase and cholinesterases. Hycanthone produced immediate side effects such as hepatotoxicity and gastrointestinal disturbances, and was consequently withdrawn. Hycanthone inhibits apurinic endonuclease-1 (APE1) by direct protein binding. Hycanthone was used in the 1980s as antitumor agents, it was pulled out of Phase II trials.

Traxoprodil (CP-101,606) is a potent, selective N-Methyl-D-aspartate (NMDA) receptor (NR2B subunit) antagonist under development by Pfizer for its potential as a neuroprotectant in head injury and neurodegenerative disease. It is in phase II trials in the US and in phase I in Japan for the potential treatment of head injury, such as, Depressive Disorder, Major and Parkinson's Disease. CP-101,606 does not protect against glutamate-induced neurotoxicity in cultured cerebellar neurons, up to a dose of 10 uM. These results are consistent with CP-101,606 being a potent NMDA antagonist, selective for the type of NMDA receptor associated with the hippocampus. Some further investigation revealed that CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.

Trazium is a putative antidepressant compound with special pharmacological effects on the catecholaminergic systems. Trazium esilate (EGYT-3615) is structurally an as-triazino isoquinolinium salt which showed considerable activity in pharmacological tests characteristic for antidepressants (antagonism of tetrabenazine, potentiation of yohimbine, behavioral despair). The compound exhibited the minimal sedative effect. The drug potentiated actions of amphetamine such as stereotypy and hypermotility. It differentially blocked the hypothermic and the stereotypy inducing action of apomorphine. Trazium esilate also inhibited the cataleptic state provoked by bulbocapnine in mice. In higher dose it decreased the plasma prolactin level in rats. Trazium esilate is a weak displacer on a1-, a2- and D2-receptors, however, it induced a2-receptor desenzitization after repeated treatment. Trazium bounds to the serum proteins and the binding was sensitive to pH and salt concentration. The binding of trazium was not saturable at a wide range of drug concentration. Trazium has both specific and non-specific binding sites on serum proteins.