Navuridine (AzddU) is a nucleoside analogue which demonstrated significant anti-HIV activity and low toxicity in preclinical studies. The drug was originally developed by University of Georgia. Navuridine is a dideoxyuridine inhibitor of HIV reverse transcriptase that is related to zidovudine. Navuridine exhibits a relatively short half-life and incomplete oral bioavailability and has not been developed into a clinical drug.

Aconiazide, the isonicotinylhydrazone of 2-formylphenoxyacetic acid, has been used in the treatment and prophylaxis of tuberculosis. Aconiazide is a pro-drug of isoniazid which was designed to be less toxic than the parent drug. Aconiazide is hydrolyzed in the body to isoniazid and 2-formylphenoxyacetic acid. 2-Formylphenoxyacetic acid has been shown to bind hydrazine and acetylhydrazine. This binding could explain the lower toxicity of aconiazide and also could provide a reason for postulating its lack of carcinogenicity.

Idronoxil (Phenoxodiol) is a synthetic flavonoid derivative developed by MEI Pharma for cancer treatment. Idronoxil inhibits proliferation of many cancer cell lines and induces apoptosis by disrupting FLICE-inhibitory protein, FLIP, expression and by caspase-dependent and -independent degradation of the X-linked inhibitor of apoptosis, XIAP. In addition, Idronoxil sensitizes drug-resistant tumour cells to anticancer drugs including paclitaxel, carboplatin, and gemcitabine. The antiproliferative effects of Idronoxil are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells. Idronoxil displays anti-cancer activity against all forms of cancer tested in vitro and in vivo to date, using cells representative of all major forms of cancer. While having a modest ability to kill cancer cells(IC50 range between about 1-5 uM), preclinical studies point to its optimal use being to sensitize cancer cells to the toxic effects of standard therapies (chemotherapy and radiotherapy). The rationale is that a sub-lethal inhibitory effect on sphingosine kinase activity reduces the ability of the cancer cell to operate drug-resistance mechanisms and to effect repair of drug- or radiation-induced damage to DNA. In the case of cytotoxic drugs such as cisplatin, carboplatin, paclitaxel, Doxorubicin, and gemcitabine, Idronoxil is an exquisite sensitizer, increasing the cytotoxic potential of those agents by between 103 -105 times, in the process restoring sensitivity to cancer cells highly refractory to those agents.

Cadazolid is a new antibiotic in development for the treatment of Clostridium difficile-associated diarrhea. Cadazolid is active against all (including linezolid- and moxifloxacin-resistant) Clostridium difficile strains. In phase I and II clinical trials, cadazolid was shown to be safe, well tolerated, and efficacious positioning itself as a potential future viable therapeutic option for CDI. Using a series of macromolecular labeling, in vitro transcription/translation, and topoisomerase studies, it was determined that protein synthesis inhibition via the oxazolidinone moiety is the primary mechanism of action of cadazolid. Cadazolid is in phase III clinical trials by Actelion Pharmaceuticals for the treatment of Clostridium difficile infection. The US FDA has designated cadazolid as both a Qualified Infectious Disease Product (QIDP) and a Fast Track development program for this indication.

Diaziquone is an aziridinylbenzoquinone with properties suggestive of an alkylating agent. The drug has shown broad antitumor activity against numerous transplantable murine tumors including curative activity against several intracerebrally implanted tumors. Diaziquone is rapidly and extensively metabolized by the liver. Diaziquone is a potent marrow suppressive agent inducing significant degrees of leukopenia, granulocytopenia, and thrombocytopenia in humans. Thrombocytopenia is often severe. Diaziquone alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. This agent can also form free radicals, thereby initiating DNA damage via DNA strand breaks. Due to its lipophilicity, diaziquone readily crosses the blood brain barrier. In phase I and preliminary phase II trials, diaziquone has demonstrated activity against primary brain tumors. Little activity has been seen in other tumor categories.

FLUMECINOL, a benzhydrol derivative, is a hepatic microsomal drug-metabolizing enzyme inducer. It was in clinical development for the treatment of pruritus associated with primary biliary cirrhosis.

Fenretinide (4-HPR) is an orally-active synthetic phenylretinamide analogue of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. Fenretinide binds to and activates retinoic acid receptors (RARs), thereby inducing cell differentiation and apoptosis in some tumor cell types. This agent also inhibits tumor growth by modulating angiogenesis-associated growth factors and their receptors and exhibits retinoid receptor-independent apoptotic properties. Phase III clinical trial data has suggested that fenretinide reduces breast cancer relapse in pre-menopausal women. Fenretinide is the most studied retinoid in breast cancer chemoprevention clinical trials due to its selective accumulation in breast tissue and its favorable toxicological profile. This agent showed a significative reduction of the incidence of second breast tumors in premenopausal women confirmed after 15-year followups. Fenretinide, a drug being developed by Sirion Therapeutics, slowed the progression of advanced dry age-related macular degeneration (AMD) by 45 percent for people receiving a higher dose of the treatment in a Phase II clinical trial. Sirion has been granted a Fast Track designation for the treatment by the FDA. Fenretinide is in phase II clinical trials for the treatment of B-cell lymphoma, chronic lymphocytic leukemia. It is also in phase I clinical trials for the treatment of cystic fibrosis.

Growth hormone releasing hexapeptide (GHRP-6) is a synthetic met-enkephalin analog that induces the release of growth hormone in vivo through binding of the ghrelin receptor. GHRP-6 increases proliferation in astrocytes through a mechanism that involves PI3K/Akt signaling. GHRP-6 also inhibits development of restraint stress-induced gastric lesions and reverses ovariectomy-induced effects on serum glucose and insulin levels. Additionally, GHRP-6 decreases locomotor activity and increases food intake in vivo. Essentially a synthetic version of ghrelin analogue, GHRP-6 (like GHRP-2) stimulates the release of an endogenous growth hormone (GH) within the somatotropes of the anterior pituitary in the animal and human body. Specifically, GHRP-6 will increase the number of somatotropes in a GH pulse by limiting the amount of somatostatin present, while standard GHRH increases the amplitude at which the pituitary cells pulse. Unlike ghrelin, GHRP-6 is not specifically used to increase appetite, but it may have secondary actions that impact hypothalamic neurons. These effects last for approximately an hour after the initial application, which mimics the natural application of GH, and consists of an eight hour circulation period. In studies GHRP-6 has shown biological actions similar to the naturally occurring hunger stimulating peptide ghrelin. Its main use is to promote food intake by stimulating hunger and aid in energy metabolism. It can be used in the treatment of GH deficiency as well as cachexia, eating disorders and obesity. GHRP-6 is a synthetic met-enkephalin (a naturally occurring opioid growth factor) analog. GHRP-6 contains D-amino acids that are entirely synthetic, lacks opioid activity, and shares no sequence relation with GHRH. It has also been shown that GHRP-6 can lead to re-stimulation of the natural production of HGH. Studies have shown that GHRP-6 increases the secretion of IGF-1 (InsulinLike Growth Factor 1) by the liver, which is speculated to be a required component in the anabolic mechanisms leading to the action of HGH. It also appears that GHRP-6 has positive implications for the central nervous system, as ghrelin is known to protect neurons.