PF-04620110 is an orally active, selective and potent DGAT1 (Acyl-CoA:diacylglycerol acyltransferase 1) inhibitor that inhibits triacylglycerol synthesis in cells and in rodents. PF-04620110 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of ≥0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, PF-04620110 has been advanced to human clinical studies. PF-4620110 had been in phase I clinical trials by Pfizer for the treatment of type 2 diabetes. But this research was discontinued in 2011.

GI-181771X is part of a class of organic compounds known as benzodiazepines. It is a cholecystokinin 1 receptor agonist investigated by GlaxoSmithKline for the treatment of obesity. In one study, GI181771X did not reduce body weight and had no effect on waist circumference or other cardiometabolic risk markers. This negative result was later assigned to an inadequate trial design rather than compound activity. Gastrointestinal side effects were more common with GI181771X than with placebo treatment. Also, in rodents, morphological changes in the pancreas were observed after administration of GI-181771X, including necrotizing pancreatitis, acinar cell hypertrophy/atrophy, zymogen degranulation, focal acinar cell hyperplasia, and interstitial inflammation. In contrast however, pancreatic changes were not observed in monkeys or in human obese patients (in a clinical trial).

N6022 is a novel, first-in-class drug with potent reversible inhibitory activity against S-nitrosoglutathione reductase (GSNOR) and a potential agent for the treatment of acute asthma and cystic fibrosis (CF). Decreased levels of GSNO in the lungs of asthmatics and cystic fibrosis patients have been attributed to increased GSNO catabolism via GSNO reductase (GSNOR) leading to loss of GSNO- and NO- mediated bronchodilatory and anti-inflammatory actions. N6022 restore GSNO levels by inhibiting GSNOR. Inhibition of GSNOR by N6022 has shown safety and efficacy in animal models of asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease. N6022 reduced bronchoconstriction and pulmonary inflammation in a mouse model of asthma. The significant bronchodilatory and anti-inflammatory actions of N6022 in the airways are consistent with restoration of GSNO levels through GSNOR inhibition.

Wilex developed WX-UK1 as a specific inhibitor of human trypsin-2, human trypsin-3 and urokinase-plasminogen activator. WX-UK1 participated in phase I clinical trial in combination with capecitabine in advanced malignancies to determine the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics. However, in April 2014, the clinical development of this drug was discontinued, as part of a company restructure.

Allergan was developing the proton pump inhibitor AGN-201904 as an enteric-coated formulation for the treatment of gastric ulcer disease. AGN-201904 is a slowly absorbed, acid-stable pro-proton pump inhibitor (pro-PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time. AGN-201904 has been used in trials studying the prevention of peptic ulcer.

1-(3,5-BIS-O-(BUTOXYHYDROXYPHOSPHINYL)-2-DEOXY-D-ERYTHRO-PENTOFURANOSYL)-5-METHYL-2,4(1H,3H)-PYRIMIDINEDIONE (Nu-3), a Bisphosphocins, is being developed by Lakewood-Amedex (formerly Nu Pharmas), for the treatment of diabetic foot ulcer, lung infections, stomatitis. Nu-3, a novel synthetic broad-spectrum antimicrobial proven to be effective in killing a wide range of Gram-positive, Gram-negative and antibiotic-resistant bacteria, recently completed a Phase 1/2a clinical trial in patients, showing no treatment-related adverse events and a trend toward efficacy. Patients treated with 2% Nu-3 for seven days had a 65.5% reduction in ulcer area versus a 29.9% reduction in the placebo arm, as measured 14 days after treatment began. In addition, 62.5% of patients treated with 2% Nu-3 saw a reduction in the microbiological load, versus 20% in the placebo. Three additional Phase 2a adaptive arm clinical trials providing robust clinical data in areas of urgent medical need are expected to be completed by 2020.

AZD4818 was developed by AstraZeneca as CCR1 receptor antagonist for the treatment of patients with chronic obstructive pulmonary disease. The study was discontinued, because of a lack of clinical efficacy.