Inecalcitol is a calcitriol analog with potential antineoplastic activity patented by a global pharmaceutical company Laboratoire Theramex. Inecalcitol is a potent agonist of vitamin D receptor (VDR). Inecalcitol was shown to be more potent than calcitriol in decreasing tumor cell growth and inducing apoptosis in a number of different model systems including models of breast cancer, prostate cancer, and squamous cell cancer. Importantly, at the doses shown to induce tumor regression in the animal models investigated, Inecalcitol had no major effect on blood calcium levels. In this phase I study, Inecalcitol was found to be well tolerated. Currently, Inecalcitol in combination with the cytotoxic drug, decitabine is undergoing a phase II clinical trial in patients with acute myeloid leukemia who are unfit to receive standard chemotherapy.

The dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity. Orphan designation of nolatrexed was granted in the Unites States of America for treatment of hepatocellular carcinoma.

Verucerfont (formerly GSK561679), a corticotropin releasing factor (CRF) receptor 1 antagonist, is being developed by GlaxoSmithKline under the license from Neurocrine Biosciences, for the treatment of post-traumatic stress disorder and congenital adrenal hyperplasia (CAH). Verucerfont is a potent, selective CRF1 receptor antagonist (IC50 for CRF1, CRF2, and CRF-BP ~ 6.1, >1000 and >1000 nM, respectively), and is orally available and brain penetrant. Verucerfont is in phase II clinical trials for the treatment of post-traumatic stress disorder or alcoholism. The compound was also in trials for the treatment of classic congenital adrenal hyperplasia (CAH). However, this research has been discontinued. In 2015, orphan drug designation was received in U.S. for the indication.

Mocetinostat is an rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others. It is undergoing clinical trials for treatment of various cancers including bladder cancer, diffuse large B cell lymphoma, follicular lymphoma, myelodysplastic syndromes, non-small cell lung cancer. Fatigue, weight loss or anorexia were most common treatment-related adverse events.

Beloranib (also known as ZGN-433 or CKD-732), a fumagillin anticancer drug that initially was developed by CKD Pharmaceuticals for the treatment of solid tumors. Beloranib is a potent inhibitor of methionine aminopeptidase 2 (MetAP2), an enzyme that modulates the activity of key cellular processes that control metabolism. This drug was studied for the treatment of Prader-Willi syndrome and obesity caused by hypothalamic injury, including craniopharyngioma-associated obesity and severe obesity in the general population. European Commission has granted orphan drug designation for beloranib for the treatment of craniopharyngioma, a rare form of benign brain tumor and for the treatment of Prader-Willi syndrome. Beloran participated in phase III clinical trials to evaluate efficacy and safety in obese adolescent and adult subjects with Prader-Willi Syndrome, but these studies were terminated. In 2016, Zafgen, the company developed the drug, based on discussions with the regulatory authority and review of obstacles, costs and development timelines to gain marketing approval for beloranib, has decided to discontinue further development of the drug.

Linsitinib is an inhibitor of the insulin receptor and the insulin-like growth factor 1 receptor, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Linsitinib is in phase II clinical trials for the treatment of metastatic prostate carcinoma, gastrointestinal stromal tumors and other cancers. Common adverse events included fatigue, nausea hyperglycaemia and anorexia.

Loxoribine [RWJ 217C7] is an immunostimulant which was developed by Johnson and Johnson. It is a selective agonist for TLR7 (Toll-like receptor 7), which possesses antitumor and antiviral properties and was investigated in a rat model of endometriosis and in addition, in phase I of a clinical trial for patients with advanced cancer.

Implitapide is a microsomal triglyceride transfer protein (MTP) inhibitor with antihyperlipidemic activity. Microsomal triglyceride transfer protein (MTP) is essential for the synthesis of both chylomicron in the intestine and very low-density lipoprotein in the liver. In an animal model, inhibition of MTP by implitapide reduced both total cholesterol and triglyceride levels and suppressed progression of atherosclerotic lesions in apolipoprotein E knockout mice fed a Western-type diet.

Indoximod is an orally available Indoleamine 2,3-dioxigenase inhibitor. It shows higher potency in reversing IDO-mediated T cell suppression. Indoximod improves the efficacy of multiple chemotherapeutics agents and some immunological checkpoints mediators in Phase I/II clinical studies for metastatic breast cancer, metastatic melanoma, non-small cell lung cancer, primary malignant brain tumors, metastatic pancreatic cancer, as well as metastatic prostate cancer.

Linifanib (ABT-869) is a structurally novel, receptor tyrosine kinase (RTK) inhibitor that is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families, but has much less activity against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. Linifanib (ABT-869) does not have a general antiproliferative effect due to its high dose requirement. However, it may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3). Linifanib (ABT-869) was in phase III clinical trial for the treatment of hepatocellular carcinoma, but the study failed to meet the primary end point.