SNX-2112, a novel 2-aminobenzamide inhibitor of heat shock protein 90 (Hsp90) was discovered by Serenex. This drug was investigated for treatment of different cancer cell lines, including hepatocellular carcinoma cells, breast cancer cells and in combination with 5-fluorouracil in esophageal cancer. However, subsequent development has been discontinued due to ocular toxicity as identified in a phase I study.

Plevitrexed is an orally bioavailable, small molecule, non-polyglutamatable, antifolate quinazoline derivative thymidine synthetase inhibitor with potential antineoplastic activity. This compound belongs to the class of organic compounds known as hippuric acids, which consist of a benzoyl group linked to the N-terminal of a glycine. Plevitrexed is transported into the cell via the physiological reduced folate carrier (RFC) system. Intracellularly, this agent selectively binds to the folate binding site of thymidylate synthase and inhibits thymidine synthesis, which may result in DNA synthesis inhibition and apoptosis. Plevitrexed has been investigated for use/treatment in pancreatic cancer, solid tumors, gastric cancer, lung cancer, and colorectal cancer.

RG2833 is a compound originally developed by the Scripps Insitute for the treatment of Friedrick's Ataxia. RG2833 is a potent and selective inhibitor of neuronal histone deacetylase. RG2833 has been granted orphan drug status has been investigated in phase one clinical trials. There has also been proof of concept studies conducted for the treatment of Parkinson's disease.

JNJ-28312141 is an orally active colony-stimulating factor-1 receptor and FMS-related receptor tyrosine kinase-3 inhibitor. In preclinical models, JNJ-28312141 caused regression of ITD-FLT3–dependent MV-4-11 AML xenografts. The drug also suppressed the growth of H460 non-small cell lung adenocarcinoma xenografts and inhibited osteoclastogenesis and osteolysis in a rat model of metastatic bone disease.

L-aminocarnityl-succinyl-leucyl-argininal-diethylacetal (Myodur or C101) is a compound that comprise a carrier residue that is an analog of carnitine, a linker group, and a residue of a protease inhibitor comprising an acetal derivative of the aldehyde group. Myodur is a muscle cell targeted product that inhibits calpain in an effort to preserve muscle tissue. In 2006 CepTor Corporation (OTCBB:CEPO), a development-stage biopharmaceutical company focusing on cell-targeted therapeutic products for neuromuscular and neurodegenerative diseases announced that the Office of Orphan Products Development of the Food and Drug Administration (FDA) granted orphan drug designation for Myodur for both Duchenne and Becker muscular dystrophies. Myodur development has been discontinued.

Ribavirin elaidate (CP-4033; TRX-201), a Lipid Vector Technology derivative of ribavirin. It inhibits elongation factor F4E (elF4E), which stimulates cell growth. Translational Therapeutics Inc. received orphan drug status from the U.S. Food and Drug Administration (FDA) in 2011 for ribavirin elaidate in the treatment of aggressive follicular, medullary and anaplastic thyroid carcinoma.

Epitalon (amino acid sequence Ala-Glu-Asp-Gly) is a synthetic peptide that has been suggested to induce the activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin and the release of genes repressed due to the age-related condensation of euchromatic chromosome regions. The researchers who generated Epitalon also reported an inhibitory effect on the development of spontaneous tumors in mice, and claimed that it increases neuronal activity and can be used in the treatment of Retinitis Pigmentosa. The peptide is still under pre‐clinical and clinical development and thus has not been approved for any therapeutic and/or prophylactic use by any government health authority in the USA or Europe.

NSC-631570 (Ukrain) is a semisynthetic compound of thiophosphoric acid and the alkaloid chelidonine from the plant Chelidonium majus. Ukrain was promoted as a drug to treat cancer and viral infections, including HIV and hepatitis. It exerts a selective cytotoxic effect on tumor cells in vitro and in vivo and shows the ability to modulate immunocyte functions. Ukrain has been used in complementary herbal medicine for more than 20 years for the treatment of benign and malignant tumors. Thus, in unresectable advanced pancreatic cancer, Ukrain alone and in combination with gemcitabine nearly doubled the median survival times in patients suffering from advanced pancreatic cancer. Inhibition of the growth of cancer cell lines in vitro, tumor mass reductions in vivo, and partial and complete remissions in oncological patients, occur as a result of Ukrain application. The drug may interfere directly with the metabolism of cancer cells and it also improves the functioning of the host immune system. Diminished synthesis of DNA, RNA and proteins, the inhibition of cellular oxygen consumption, and the induction of programmed cell death in malignant cells have been described following Ukrain administration. The drug can also modify the immunological response via an increase in the number of total T-cells and a normalization of the T-helper/T-suppressor lymphocyte ratio. However,according to the American Cancer Society and the Memorial Sloan-Kettering Cancer Center, there is no evidence that Ukrain is an effective cancer treatment. Through an Austrian company known as Nowicky Pharma, the drug, which was never approved by regulators, was sold as a treatment for AIDS, radiation-induced diseases and as a cure for all forms of cancer. Ukrain is not approved by the Food and Drug Administration but is available in parts of Europe and from Tijuana clinics.