Cridanimod (Virexxa) is a small-molecule immunomodulator and interferon inducer, which, in preliminary studies, has been shown to increase progesterone receptor expression in endometrial tissue. Restoration of progesterone receptor expression may re-sensitize endometrial tumor tissue to progestin therapy in previously unresponsive tumors. Cridanimod was originally developed by Polysan and Pharmsynthez and licensed to Xenetic Biosciences. Virexxa is currently being studied in an ongoing Phase 2 multi-national study in conjunction with progestin therapy for the treatment of endometrial cancer in women with the recurrent or persistent disease who have failed progestin monotherapy.

Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 / dopamine D2 blocking activity. It is not available in the US but marketed in other countries for prophylaxis of a migraine, occlusive peripheral vascular disease, the vertigo of central and peripheral origin, motion sickness and as an adjuvant in the therapy of epilepsy. The drug is also investigated for the treatment of schizophrenia.

Nimorazole is an antimicrobial with activity against anaerobic bacteria and protozoa. Its actions and properties are similar to metronidazole. It has also been used in trials studying the treatment of Hypoxia, Radiotherapy, Hypoxic Modification, Gene Profile, Gene Signature, and Head and Neck Squamous Cell Carcinoma, among others. Azanta is developing, nimorazole, as an oral hypoxic radio-sensitiser for the treatment of patients with head and neck cancer who are undergoing radiotherapy. Previously, nimorazole has been approved for use as an anti-protozoal agent and has been launched worldwide. Nimorazole, for the treatment of head and neck cancer patients undergoing radiotherapy received orphan designation by EMA in 2011.

Efaproxiral is a synthetic, small molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. But no benefit was seen for efaproxiral in phase III clinical trials. The only serious adverse effect detected was hypoxaemia. Efaproxiral is explicitly excluded from the 2012 World Anti-Doping Agency list of Prohibited Substances and is explicitly included in the Prohibited Methods section M1 as a forbidden procedure to alter the oxygen-haemoglobin dissociation curve in order to allosterically modify haemoglobin.

Cepharanthine (CEP) is a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata. It has been widely used in Japan for more than 40 years to treat a wide variety of acute and chronic diseases. CEP inhibits tumor necrosis factor (TNF)-α-mediated NFκB stimulation, plasma membrane lipid peroxidation and platelet aggregation and suppresses cytokine production. It has also been shown to scavenge free radicals and to have a protective effect against some of the responses mediated by pro-inflammatory cytokines such as TNF-α, interleukin (IL)-1β and IL6. CEP has successfully been used to treat a diverse range of medical conditions, including radiation-induced leukopenia, idiopathic thrombocytopenic purpura, alopecia areata, alopecia pityrodes, venomous snakebites, xerostomia, sarcoidosis, refractory anemia and various cancer-related conditions. No safety issues have been observed with CEP, and side effects are very rarely reported. Recently was described a transcriptomic approach confirmed that cepharanthine might have a potential innovative antiplasmodial mechanism of action. Cepharanthine could interfere with several important functions for Plasmodium survival and virulence as the mitochondrion, apicoplast, cytoadherence antigenic variation and Maurer’s clefts. Thus, cepharanthine might play an ongoing role in the progress on anti-malarial drug discovery efforts. Also using intravenous and oral administration of CEP was shown its protective effect for acute or late toxicity to the bladder/urethra and rectum. It was discovered, that acute urinary toxicity was significantly milder for the intravenous group than for the oral and non-administration groups. The protective efficacy of CEP was not approved for acute rectal toxicity, but late rectal toxicity was significantly milder for the intravenous group than for the oral group. Intravenous Cepharanthin administration may prevent acute or late toxicity by radiotherapy for prostate cancer.

Ataluren (Translarna) is a small-molecule drug approved in Europe for the treatment of Duchenne muscular dystrophy caused by a nonsense mutation. Ataluren interacts with the ribosome enabling it to read through premature nonsense stop signals on mRNA and allowing the cell to produce a full-length, functional protein. Ataluren is also being tested in phase III for cystic fibrosis caused by a nonsense mutation.

Gimeracil is a component of an oral fixed combination known under the name Teysuno or S-1 (tegafur, gimeracil and oteracil potassium at a molar ratio of 1:0.4:1). The formulation was approved in Asia and Europe for the treatment of a rare condition of gastric cancer. Given in combination, gimeracil enhances the efficacy of tegafur by inhibiting dihydropyrimidine dehydrogenase, an enzyme involved in metabolism of tegafur and its active metabolite 5-fluorouracil.

Dimebon (latrepirdine) is an orally available, small molecule, gamma carboline derivative that was developed and used in Russia as an over-the-counter oral antihistamine for allergy treatment since 1980s. In 1990s it was shown that Dimebon has promising potential in treating neurodegenerative diseases. In 2003, Medivation Inc acquired the rights to Dimebon. Medivation went public in December 2004, with Dimebon as the only drug in its pipeline. The product was being developed by Medivation and Pfizer as a treatment for early-stage Alzheimer's disease and Huntington's disease. However, development was discontinued by Medivation and Pfizer in early 2012. Dimebon inhibits alpha-Adrenergic receptors (alpha1A, alpha1B, alpha1D, and alpha2A), Histamine H1 and H2 receptors and Serotonin 5-HT2c, 5-HT5A, 5-HT6 receptors with high affinity. Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition.

PR-69 (Doranidazole) is a hypoxic radiosensitizer, and is a derivative of 2-nitroimidazole intended to reduce neurotoxicity due to its blood brain barrier (BBB) impermeability. Several studies have shown that doranidazole has a radiosensitizing effect under hypoxia, both in vitro and in vivo. Based on these studies, a phase III trial of doranidazole against advanced pancreatic cancer was performed; it was demonstrated that treatment with doranidazole following radiation significantly improved the tumor mass reduction rate and extended patient survival. Various results have suggested that doranidazole has promising potential for hypoxia-targeting chemoradiotherapy.

Xenon is a noble gas used as an anesthetic agent. Xenon can associate with amino acid side chains of the active site of enzymes such as serine proteinases (including elastases and collagenases); these enzymes can form a specific binding cavity for single xenon atom without inducing major changes in protein structure. It has been demonstrated that xenon binds within the heme cavity of cytochrome P-450 monooxygenases and is capable of inhibiting the catalytic activity of some enzymes in vitro. Current evidence suggests that inhibition of N-methyl-D-aspartate (NMDA) receptor signaling is the mechanism by which xenon induces anesthesia. Although approved for use in anesthesia in Russia in 2000, it was unavailable for use in western countries until October 2005 when approval for its use was granted in Germany.