Trehalose, a naturally occurring disaccharide of glucose that appears to function in an anhydrobiotic capacity in many organisms. Bioblast Pharma study trehalose in Phase 2 for treating patients with Oculopharyngeal Muscular Dystrophy (OPMD) and spinocerebellar ataxia, type 3. In OPMD trehalose prevents the aggregation of the pathological protein (PABPN1) in muscle cells, the hallmark of the disease, by stabilizing the protein, reducing the formation of protein aggregations, and promoting their clearance from cells through autophagy, thus preventing muscle cell death. Trehalose induces autophagy via mTOR independent pathway. It activates TFEB, a master controller of lysosomal biogenesis and autophagy, by inhibiting AKT which is a negative regulator of TFEB that acts by direct phosphorylation (and inhibition) of TFEB. In addition, trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Trehalose was in phase III clinical trial to study if it was possible to use the drug as add-on therapy in Bipolar Depression. Also in combination with hyaluronate, it can be used to treat dry eye syndrome. Trehalose protects the epithelial cells on the ocular surface, improving their resistance to the daily stresses of dry environments and tear film changes in a dry eye.

Calcium-D-glucarate (also known as CALCIUM SACCHARATE) is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans. Oral supplementation of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microflora and involved in Phase II liver detoxification. Elevated beta-glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers. Other potential clinical applications of oral calcium-D-glucarate include regulation of estrogen metabolism and as a lipid-lowering. In addition, by reducing the beta-glucuronidase viability and activity of intestinal bacteria, salts of D-glucaric acid have been shown to enhance enterohepatic circulation and reduce steady state levels of cholesterol synthesis, resulting in decreased serum lipid levels.

Iclaprim is an investigational broad-spectrum diaminopyrimidine antibiotic in development for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Iclaprim acts on bacterial cells by competitively inhibiting dihydrofolate reductase (DHFR), a key enzyme in the folate cycle; the same mode of inhibition is exerted by trimethoprim. Iclaprim resistance is mainly determined by point mutations in the dfr gene as studied in S. aureus and S. pneumoniae. Surveillance studies demonstrate that the spectrum of activity of iclaprim includes many organisms indicated in cSSSI including S. aureus and S. pyogenes. Iclaprim is bactericidal in vitro, generally at concentrations equal to the MIC that are maintained in human plasma for several hours after a therapeutic dose. Bactericidal activity is primarily time-dependent and concentration independent. Due to its structural similarity with trimethoprim, iclaprim is synergistic with sulfonamides against a broad spectrum of bacterial species. The antimicrobial mechanism of action of iclaprim is mediated by competitive inhibition of bacterial DHFR, the same mode of inhibition exerted by TMP. The activity of iclaprim against TMP-R mutants of S. aureus and S. pneumoniae is attributable to additional hydrophobic interaction between iclaprim and the enzyme. The same mechanism of action of iclaprim, competitive inhibition with the natural substrate DHF, is seen against both TMP-S and -R enzymes. Iclaprim is well suited for use as a first-line empiric monotherapy in patients with ABSSSI who are comorbid with renal impairment for the following reasons. n July 2015, the U.S. Food and Drug Administration, or FDA, designated the IV formulation of iclaprim as a Qualified Infectious Disease Product (QIDP) for ABSSSI and HABP. QIDP status grants iclaprim regulatory Fast Track designation, Priority Review and, if approved, a five-year extension to the statutory market exclusivity period in the United States, resulting in 10 years of market exclusivity from the date of approval.

Pibutidine hydrochloride (IT-066), a novel histamine H2 receptor antagonist has powerful and long lasting antisecretory and antiulcer effects and is a useful antisecretory drug for treatment of peptic ulcer diseases.

NS-3 (montirelin, CG 3703) is an analog of thyrotrophin releasing hormone (TRH). More potent and longer acting than TRH, CG-3703 produced beneficial effects in animal models of concussion-induced unconsciousness, cerebral ischemia, memory disruption, spontaneous convulsions in rats, narcolepsy, and spinal trauma. Given its efficacy in these models, the potential indications were broadened to include seizures, nerve trauma, cognitive dysfunction, and sleep apnea.

Tezosentan (Veletri; Ro 61–0612) is a dual endothelin receptor antagonist that has been shown to improve cardiac output, decrease pulmonary capillary wedge pressure, and reduce pulmonary and systemic vascular resistance in initial clinical studies in acutely decompensated heart failure. Tezosentan is a water-soluble ET-1 receptor antagonist with high affinity to both ETA and ETB receptors but greater potency for the ETA receptor subtype. Clinical studies demonstrated mixed results for Tezosentan regarding its efficacy and tolerability in the management of decompensated heart failure. The side effects of Tezosentan include a headache, nausea, and hypotension.

Lazabemide is a reversible and selective inhibitor of monoamine oxidase B (MAO-B) that was under clinical development against Parkinson's disease, Alzheimer's disease and as an aid to smoking cessation. The development of the drug was discontinued due to liver toxicity.

Atamestane is a new, competitive, and irreversible inhibitor of estrogen biosynthesis. It is an aromatase inhibitor. Atamestane lacks other intrinsic hormonal or antihormonal activities and shows no inhibition of other cytochrome-P450 dependent enzymes of adrenal steroidogenesis. It had been in phase III clinical trial for the treatment of breast cancer and phase II for the treatment of benign prostatic hyperplasia. It was discontinued from development after an 865-patient trial in breast cancer showed no improvement in efficacy over letrozole.

Broxuridine (5-Bromo-2-deoxyuridine, BrdU) is a thymidine analogue that is incorporated into replicating DNA. BrdU taken up by cells is phosphorylated and incorporated into DNA in place of dT. Although originally designed as a chemotherapeutic agent, sublethal concentrations of BrdU have long been known to alter the growth and phenotype of a wide range of cell types. The most popular use of BrdU is as a tracer of DNA synthesis. The other well-known use of BrdU is as a DNA photosensitizer. BrdU substitution of dT in DNA sensitizes it to near-UV light, and cells with BrdU-substituted DNA cannot survive after exposure to near-UV light. BUdR has side effects on cell functions. Cell growth can be inhibited, normal development of differentiating systems be perturbed, activities of specific enzymes be reduced. Mutagenic effects of BUdR are interpreted as reflections of a mispairing of BUdR in its rare enol form. Effects of BUdR which can be reversed by addition of thymidine are not likely to be mutagenic. As another mechanism of action of BUdR has been suggested that incorporation of BUdR into DNA alters the pattern of transcription.

Dexloxiglumide is a selective antagonist of cholecystokinin receptor A (CCKA, CCK1). It is the dextro isomeric form of loxiglumide, Dexloxiglumide was investigated for treatment of irritable bowel syndrome. Its development in USA was discontinued.