NMED-160 (also known as MK-6721, NP-118809, Z-160) is a potent N-type calcium channel blockers, which has good selectivity over L-type calcium channels. Neuromed Pharmaceuticals developed this compound for the treatment of the chronic pain. However, that study was discontinued in 2007 in spite of absence of adverse events, but because drug did not demonstrate the ideal, pharmaceutical characteristics considered necessary to advance the compound further in development. Then Zalicus, Inc. was developing that drug for the treatment of chronic neuropathic pain associated with lumbosacral radiculopathy and post-herpetic neuralgia and drug was in the phase II clinical trial. Nevertheless, based on the result from trials, where Z160 did not meet the primary endpoint, Zalicus was also discontinuing the Z160 program.

CTS-1027 (Ro-1130830) is a hydroxamic acid matrix metalloprotease (MMP) inhibitor. CTS-1027 was originally designed as a strong inhibitor of MMP-2, -3, -8, -9, -12, -13 and -14, without inhibiting MMP-1 and MMP-7. CTS-1027 was proved to be safe in clinical trials for osteoarthritis conducted by Roche. CTS-1027 was then licensed from Roche to Conatus Pharmaceuticals and was investigated as a protector from liver fibrosis in hepatitis C virus patients. The development of the drug was discontinued due to laboratory abnormalities and adverse events in a subset of clinical trial participants.

R-etodolac (SDX-101) is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid). The absolute configuration of the enantiomer is R-(-)-etodolac. R-etodolac specifically bound retinoid X receptor (RXRalpha), inhibited RXRalpha transcriptional activity, and induced its degradation by a ubiquitin and proteasome-dependent pathway. In addition R-etodolac can disrupt the beta-catenin signaling pathway. R-etodolac exerts antineoplastic properties. R-etodolac was in phase 2 studies for the treatment of hematologic malignancies however development was discontinued.

Cobristone is a locally acting chloride channel activator that works to stimulate and protect the mucosal barrier function. Cobristone is being developed by the Sucampo Pharmaceuticals, Inc. for the prevention of oral mucositis and for the treatment of non-erosive reflux disease (NERD), a major subtype of gastroesophageal reflux disease. The development of the drug was terminated after phase 2 clinical trials failed to meet its primary endpoints.

Atrasentan (ABT-627, A-127722) is a selective endothelin A receptor antagonist. Atrasentan is being developed by AbbVie as an oral treatment for diabetic nephropathies.Abbott Laboratories was conducting clinical development of atrasentan for the treatment of certain cancers, including phase II trials for prostate cancer. However, no recent development has been reported for cancer indications and development is presumed to be discontinued.

2-Methoxyestradiol (2ME2) is a natural metabolite of endogenous estrogen hormone 17β-estradiol in human and devoid of estrogenic activity. It is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It has undergone Phase 1 clinical trials against breast cancers. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. 2-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. 2-Methoxyestradiol shows strong cytotoxic effect on estrogen dependent and independent cancerous cells, which is mainly due to disruption of microtubule process and p53 induced apoptosis through caspase, reactive oxygen species (ROS), superoxide dismutase (SOD) and nitric oxide synthase. 2-Methoxyestradiol inhibits tubulin polymerisation by binding to colchicine binding site of the tubulin and arrests cell cycle at G2/M-phase.

Ammonium trichlorotellurate (AS-101) is a synthetic non-toxic tellurium derivative, structurally similar to cisplatin, with immunostimulatory and anti-hair loss properties. Ammonium trichlorotellurate induces production of colony stimulating factor (CSF), interleukin-2 (IL-2), and IL-2 receptors by increasing the calcium ion influx through the cell membrane and subsequently exerts its immunostimulatory effects through the CSF-mediated increase in macrophage/granulocytes. This agent is also a potent inducer of interferon and a spectrum of cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF). In animal studies, ammonium trichlorotellurate exerts its anti-hair loss effect by inducing anagen and obstructing spontaneous catagen via promoting follicular keratinocyte proliferation and interfering with terminal differentiation, respectively. AS-101 suppresses production of HIV-1. It inhibited reverse transcriptase activity and replication of human immunodeficiency virus type 1. RDDP and DDDP activities were impaired by the drug with calculated IC50 value of about 4 uM. Intravenous AS-101 was in trials in patients with HIV infections. AS-101, a small-molecule integrin αvβ3 and VLA-4 inhibitor is being developed by BioMAS in Israel for the treatment of genital warts, age-related macular degeneration and fertility preservation. Phase II clinical trials are ongoing. The drug was also undergoing phase II development in acute myeloid leukaemia, atopic dermatitis, chemotherapy-induced damage, myelodysplastic syndromes, thrombocytopenia, alopecia, psoriasis. However, development for these indications was discontinued.

Filanesib is a highly selective, targeted KSP inhibitor with a mechanism of action distinct from currently available myeloma therapies such as immunomodulatory drugs (IMiDs®) and proteasome inhibitors. Across multiple studies, filanesib has demonstrated activity in heavily pretreated multiple myeloma patients, with a consistent safety profile including no drug-induced peripheral neuropathy and limited non-hematologic toxicity. Adverse events are generally limited to transient, non-cumulative and predominantly asymptomatic myelosuppression (decreases in blood counts) when supportive measures are used. Alpha 1-acid glycoprotein (AAG), a plasma protein, is a potential patient selection marker for filanesib. AAG is undergoing further investigation in clinical trials and could represent the first patient selection marker for a myeloma therapy. Filanesib is in Phase II for Multiple myeloma treatment.

CPG-52852 (PF-04878691) is a toll-like receptor 7 (TRL7) agonist. The drug was developed by 3M Pharmaceuticals and the Coley Pharmaceutical Group and was investigated in a number of clinical trials in patients with advanced cancer. Sustained tolerability and modest clinical benefit were demonstrated in heavily pretreated recurrent breast, ovarian, and cervix cancers. After Coley was acquired by Pfizer in 2007, the drug was repurposed for the treatment of hepatitis C. A phase 1 clinical trial was conducted. The development of the compound was discontinued because the compound was believed to unlikely to achieve the proof-of-concept criteria as a result of pharmacodynamic modeling.

Marizomib is a natural beta-lactone produced by the marine bacterium Salinispora tropica. Marizomib has a broad inhibition profile for the 20S proteasome and has been shown to inhibit the CT-L (beta5) CT-T-laspase-like (C-L, beta1) and trypsin-like (T-L, beta2) activities of the 20S proteasome. The drug is being tested in phase II clinical trials for the treatment of Multiple Myeloma and Malignant Glioma and in phase I in patients with Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma