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.

Sobetirome (3,5-dimethyl-4[(4'-hydroxy-3'-isopropylbenzyl)-phenoxy] acetic acid, also known as GC-1 and QRX-431, is a member of a class of compounds known as selective thyromimetics. It was firstly developed by Thomas Scanlan’s group at the University of California-San Francisco (UCSF) in 1995. Sobetirome binds selectively to the main hepatic form of thyroid hormone (TH) receptor, TRβ1, compared to TRα1, which is principally responsible for thyrotoxic effects on heart, muscle and bone. Sobetirome also preferentially accumulates in liver. It was originally envisaged that sobetirome could be used to stimulate hepatic pathways that lower cholesterol without harmful side effects and might be used in conjunction with statins. Indeed, sobetirome progressed through preclinical animal studies and Phase I human clinical trials with excellent results and without obvious harmful side effects. Sobetirome had been in phase I clinical trials for the treatment of lipid metabolism disorders and obesity. However, this research has been discontinued.

Cilengitide is a cyclized Arg-Gly-Glu (RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins. Its precursor was first synthesized in 1995 as c(RGDfV), and later modified by the incorporation of N-methyl Val c(RGDfMetV), generating the current form of the drug. Cilengitide displays subnanomolar antagonistic activity for αvβ3 and αvβ5, and is the first integrin antagonist evaluated in clinical phase I and II trials for treatment of glioblastoma and several other tumor types. Cilengitide-induced glioma cell death and inhibition of blood vessel formation may use different molecular mechanisms, including regulation of tumor hypoxia and activation of apoptotic pathways. Cilengitide inhibits cell signaling through FAK-Src-Akt and Erk mediated pathways in endothelial and tumor cells and attenuates the effect of VEGF stimulation on growth factor signaling. Cilengitide has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide.

Ritanserin (INN, USAN, BAN) is a serotonin receptor antagonist which was never marketed for clinical use but has been used in scientific research. In humans, ritanserin increases deep slow-wave sleep, improved liveliness in a variety of psychiatric disorders and facilitated participation in behaviour therapy. During clinical trials, unexpected observations indicated that ritanserin may be of value in treating obsessive-compulsive disorder, acute mania, negative symptoms of schizophrenia, drug addicts, etc. Clinical observations confirmed the efficacy of ritanserin in the chronic withdrawal phase after detoxification from ethanol. Ritanserin had been in phase III clinical trials by Janssen L.P. for the treatment of anxiety disorder and major depressive disorder. However, the clinical development of ritanserin was discontinued.

Paquinimod is an immunomodulatory compound preventing S100A9 binding to TLR-4. It was studied in experimental osteoarthritis, in patients with mild active systemic lupus erythematosus and in systemic sclerosis patients. In January 2014, the US FDA granted orphan drug designation to paquinimod for the treatment of systemic scleroderma. The Orphan designation is implemented to promote the development of drugs that may provide significant benefit to patients suffering from rare diseases identified as life threatening or chronically debilitating. The further development of paquinimod for systemic lupus erythematosus and rheumatoid arthritis was discontinued.