Avasimibe (CI 1011) is a potent ACAT (Acyl-CoA:cholesterol acyltransferase) inhibitor. Avasimibe inhibits both ACAT1 and ACAT2 isoforms. Avasimibe was in development by Parke-Davis (now Pfizer) in the US for the treatment of atherosclerosis and hyperlipidaemia. Avasimibe was in phase III studies and more than 1300 patients had been treated for up to one year, however, in October 2003, Pfizer announced that development had been discontinued.

Pantetheine is the mercaptoethyl conjugated amide analog of pantothenic acid (Vitamin B5), an intermediate in the production of coenzyme A by the body. Pantetheine is part of two larger compounds (coenzyme A and acyl-carrier protein) that promote a large number of metabolic reactions essential for the growth and well-being of animals. Pantetheine has been found to ameliorate symptoms in various disease models but specifically in Pantothenate Kinase-Associated Neurodegeneration (PKAN). Pantetheine is usually administered in its disulfide form (i.e. pantethine) since pantethine is commercially available and is reduced to pantetheine in biological systems and pantethine was hydrolyzed to pantetheine and pantothenic acid prior to absorption. The applicability and efficacy of pantethine (therefore also pantetheine) as a clinical therapeutic however is hampered since both forms can be degraded by pantetheine present in the body.

(+)-selfotel ((+)-CGS-19755) is an enantiomer of selfotel, a competitive antagonist at N-methyl-D-aspartate (NMDA)-preferring receptors. The inhibition of NMDA-evoked ACh release from rat striatal slices is stereospecific, with the (+)-enantiomer less potent than the (-)-enantiomer.

Evofosfamide, also formerly known as TH-302, is an investigational hypoxia-activated prodrug and is used to target cancerous cells under hypoxic conditions, which is a feature possessed by multiple solid tumors including glioblastoma and pancreatic cancer. Within regions of tumor hypoxia, evofosfamide releases bromo isophosphoramide mustard (Br-IPM), a potent DNA alkylating agent that kills tumor cells by forming DNA crosslinks. Once activated in hypoxic tissues, Br-IPM can also diffuse into surrounding oxygenated regions of the tumor and kill cells there via a “bystander effect”. Because of its preferential activation in the targeted hypoxic regions of solid tumors, evofosfamide may be less likely to produce broad systemic toxicity seen with untargeted cytotoxic chemotherapies.

NB-001, an oil-in-water emulsion containing high energy nanometer-sized droplets stabilized by surfactants is designed for topical treatment of herpes labialis infections. NB-001 diffuses through the stratum corneum via the follicular route to accumulate in the epidermal and dermal tissues, without disrupting the normal epithelial matrix. The concentrations achieved in the epidermis and dermis are well above the concentrations required for antiviral activity.

Icaritin is a monoprenylated favonol with 4′-methoxyl from Epimedium Genus. It has been documented to have osteoblastic and neuroprotective activities. It can reduce the incidence of steroid-associated oesteonecrosis in rabbit with inhibition of both intravascular thrombosis and extravascular lipid deposition for maintaining the integrity of intraosseous vasculature. Icaritin shows anti-infammatory activity and inhibitory activities against cancer cells. The phase III clinical trial is planned for the treatment of Hepatocellular carcinoma.

Fipamezole is a fluorine substituted imidazole compound with high antagonist specificity for the presynaptic alpha2-adrenoceptor. There were no significant differences between the affinity of Fipamezole for the different subtypes, thus characterizing Fipamezole as a non-subtype–selective alpha2 antagonist. Fipamezole had been in phase III clinical trials for the treatment of dyskinesia associated with Parkinson’s disease. Detected side effects are hypertension, nausea, vomiting, dysgeusia, facial flushing.

Lixivaptan is an orally-active, vasopressin 2 receptor antagonist. It is indicated for the treatment of symptomatic hypervolemic and euvolemic hyponatremia, associated with heart failure (HF) and syndrome of inappropriate antidiuretic hormone (SIADH). Adverse events likely to be result of the pharmacologic action of lixivaptan are: constipation, dry mouth, dizziness, insomnia. Grapefruit juice significantly increased the extent of lixivaptan absorption as compared to lixivaptan administered under fasted conditions but not under fed conditions. Lixivaptan Cmax and AUC∞ increased by 2.4-fold and 3.2-fold, respectively, when lixivaptan was administered with ketoconazole (the same in case of Simvastatin).

Flumatinib (HHGV678) is an orally bioavailable antineoplastic tyrosine kinase inhibitor. Flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. Flumatinib was extensively metabolized after oral administration, and the major metabolic pathways observed were amide hydrolysis, demethylation, oxidation, and glucuronide conjugation. It is in phase III clinical trials for the treatment of Chronic myeloid leukemia (in China).

Apabetalone (RVX-208) is a small molecule BET bromodomain inhibitor selective for BRD4-BD2 undergoing clinical development as a potential therapy to enhance ApoA-I production and treat atherosclerosis and prevent cardiovascular disease events. Apabetalone increases apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-Cholesterol) in vitro and in vivo which is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increased the Tm of all BET bromodomains, indicative of binding. RVX-208 competes for acetylated histone H4 peptide binding to both bromodomains of BRD4, similar to JQ-1, but with a preference for BD2 over BD1. RVX-208 also binds to the bromodomains of BRDs 2 and 3 with a similar preference for BD2 (Kd~5–30 nM) over BD1 (Kd~2–3 uM). Treatment of humans for 1 week with oral RVX-208 increased apoA-I, pre-beta-HDL, and HDL functionality. Resverlogix Corp. has commenced a Phase 3 clinical trial in cardiovascular disease patients with type 2 diabetes mellitus with a primary endpoint of time to first occurrence of Major Adverse Cardiac Events (MACE).