Decoglurant is a negative allosteric modulator of the mGlu2 and mGlu receptors developed by Roche. Decoglurant was investigated in a phase 2 clinical trials in patients with major depressive disorder. Negative results were reported and the development was discontinued in 2015.

Rigosertib sodium (ON 01910.Na) is a small molecule inhibitor of critical pathways important in the growth and survival of cancer cells, being developed by Onconova Therapeutics ("Onconova") for the treatment of hematologic malignancies and solid tumors. Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Extensive Phase I and Phase II studies with rigosertib have been conducted at leading institutions in the U.S. and abroad in more than 450 patients with solid tumors and hematological cancers, including MDS and AML. MDS and AML are blood disorders widely recognized as difficult to manage, with limited therapeutic options available for patients, especially those with drug-resistant disease. The multi-site Phase III ONTIME trial in MDS patients is under a Special Protocol Assessment (SPA) from the U.S. FDA and is being supported by an award from the Therapeutics Acceleration Program (TAP) of the Leukemia and Lymphoma Society (LLS). FDA has granted Orphan Drug Designation for the use of rigosertib in MDS. The clinical program in solid tumors is also advancing with initiation of the Phase II/III combination ONTRAC trial (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer) and Phase II single agent trial in ovarian cancer. In Japan, SymBio is developing rigosertib for the treatment of refractory/relapsed HR-MDS (IV form) and first-line LR-MDS (oral form).

Gemcitabine elaidate is an ester of anticancer drug gemcitabine and elaidic fatty acid. The motivation to make an ester was to facilitate gemcitabine uptake and prolong retention in the cell. The drug is converted to parent compound gemcitabine both inside and outside the cell. Gemcitabine elaidate was developed by Clavis Pharma for treatment of solid tumors, including non-small cell lung cancer and pancreatic cancer, but its development was discontinued after product missed the primary endpoint in the Phase II LEAP trial to treat metastatic pancreatic cancer.

FLUCICLATIDE F-18 is an 18F-radiolabelled synthetic cyclic peptide containing an RGD motif (Arg-Gly-Asp). It may be used as a tracer in positron emission tomography (PET) imaging. The RGD motif of FLUCICLATIDE F-18 selectively binds to the alpha-V/beta-3 integrin, upregulated on tumor cells and endothelial cells of tumor vasculature. Integrins play an important role in tumor angiogenesis and metastasis. Thus, FLUCICLATIDE F-18 is a potential biomarker of therapeutic response to antiangiogenic inhibitors.

Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway, which is over-activated in many types of cancer and has been shown to be an important pathway in cancer stem cell-mediated propagation of cancer. Napabucasin has already shown promising efficacy on different cancer types, both as a monotherapy and in combination with conventional chemotherapeutic agents. Early-phase trials have shown promising anti-tumor efficacy when patients are treated with napabucasin in combination with standard chemotherapy agents, and preclinical results suggest that napabucasin can synergize with chemotherapy agents, such as paclitaxel, to potentially overcome drug resistance. Encouraging phase Ib/II trial results warrant further clinical study with napabucasin and paclitaxel combination therapy, especially in malignancies where there is an urgent and unmet need for effective therapeutics, such as in patients with advanced pancreatic adenocarcinoma.

LADARIXIN is a dual inhibitor of chemokine receptors CXCR1 and CXCR2. It inhibits human polymorphonuclear leukocyte (PMN) migration to chemokine CXCL8 in vitro and prevents PMN infiltration and tissue damage in several models of cerebral ischemia/reperfusion in vivo. It is under development for the treatment of type 1 diabetes.

CAT-1004 (Edasalonexent)is an orally administered small molecule designed to inhibit NF-κB, which is activated from infancy in Duchenne muscular dystrophy and is central to causing muscle damage and preventing muscle regeneration. Structurally CAT-1004 represents covalently links salicylic acid and docosahexaenoic acid -- two compounds known to inhibit NF-κB. . In a Phase 1 study in adults, NF-κB activity in peripheral mononuclear cells was inhibited following a single dose of edasalonexent but not by equimolar doses of salicylic acid and docosahexaenoic acid. Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy, which occurs early in the disease process and precedes loss of muscle function. Salicylic acid prevents NF-κB mediated muscle atrophy and decreases protein catabolism in muscle. Docosahexaenoic acid has been shown to upregulate anti-inflammatory pathways and suppress pro-inflammatory pathways via modulation of NF-κB activity. Edasalonexent is endocytosed and hydrolyzed by intracellular fatty acid amide hydrolase (FAAH) to release salicylic acid and DHA in the intracellular compartment, thus having a potential advantage of selectively delivering higher doses in target muscle cells where FAAH is abundant.

(-)-Epigallocatechin is a polyphenol, which occurs naturally in various plants, including green tea leaves. The compound was shown to have anti-cancer activity in vitro, with breast cancer, lung cancer, and colon cancer cells. The commercial preparation of Polyphenon E contains about 3% (-)-epigallocatechin as an impurity.