E-3710 (Z-215) is a new proton pump inhibitor (PPI). E-3710 irreversibly inhibited H(+),K(+)-ATPase activity in pig gastric vesicles with an acidic internal environment. E-3710 is a long-acting inhibitor of gastric acid secretion and a promising novel therapy for acid-related diseases, such as gastroesophageal reflux disease. E-3710 is metabolized through oxidation, reduction and conjugation. Unchanged E-3710 was excreted in urine at trace levels but was not detected in faces. The major isozyme contributing to the oxidation of Z-215, including the formation of Z-215 sulphone, was CYP3A4. It is useful for treating gastroesophageal reflux disease in all CYP2C19 genotypes. E-3710 is in phase II clinical trial for the treatment of erosive esophagitis and gastro-esophageal reflux.

LX-7101 (Lexicon Pharmaceuticals) was advanced to Phase-I clinical trials for treatment open-angle glaucoma or ocular hypertension. This drug is a potent inhibitor of LIM-kinase 2 (LIMK2) kinase and inhibits to less extent LIMK1 and Rho-associated protein kinase 2 (ROCK2).

Squaric acid is a dibasic organic acid and useful intermediate in a variety of synthetic reactions involving the synthesis of photosensitive squarylium dyes and inhibitors of protein tyrosine phosphatases. Medically, squaric acid dibutyl ester or dibutyl squarate derives from a squaric acid is used for the treatment of warts.

Fluoroacetic acid F-18 (18F-Fluoroacetate,18F-FAC) is an analog of acetate with a longer radioactive half-life (18F=110 min). Fluoroacetic acid F-18 was under investigation as a PET imaging agent. 18F-FAC was considered a promising alternative to 11C-ACE for positron tomographic imaging of prostate cancer, and possibly of other neoplasms with relatively low glucose use.

Vedroprevir, or GS-9451, is a potent inhibitor of the HCV NS3 protease (Box 1). NS3 is a serine protease that cleaves the HCV polyprotein and helps generate the viral replication complex. Through binding NS3, vedroprevir halts the assembly of the viral replication complex, thus interfering with the assembly and release of viral particles. Vedroprevir is a potent inhibitor of NS3 protease with high selectivity against off-target proteases. It has rapid association kinetics and slow dissociation kinetics. Preclinical studies of vedroprevir showed high oral bioavailability in rats, dogs, and monkeys. Preclinical studies of vedroprevir demonstrated potent NS3 inhibition using laboratory strains as well as patient-derived NS3 protease gene isolates. In a phase I, randomized trial of vedroprevir monotherapy, doses of 200 and 400 mg/day yielded median maximal HCV RNA reductions of −3.2 log10 in genotype 1a patients and −3.5 log10 in genotype 1b patients. Significantly less activity was seen against genotype 2a HCV when compared to genotype 1. Vedroprevir was not listed on the Gilead Sciences pipeline in its 2014 annual report and appears to have been discontinued for the once-daily treatment of Hepatitis C.

4,4’-Diamino-2,2’-stilbenedisulfonic acid (also known as amsonic acid) is used in the synthesis of dyes and optical brighteners or fluorescent whitening agents. Amsonic acid possesses estrogenic activity, and thus provided a possible mechanistic explanation for the complaints of impotency in factory workers exposed to this compound. In the 2-year feed studies on rodents, there was no evidence of carcinogenic activity of amsonic acid, in male or female F344/N rats receiving 12,500 or 25,000 ppm. In addition, there was no evidence of carcinogenic activity of this compound in male or female B6C3F1 mice receiving 6,250 or 12,500 ppm.

PCI-27483 is a reversible small-molecule inhibitor of activated factor VII (factor VIIa) with potential antineoplastic and antithrombotic activities. FVII, a serine protease, becomes activated (FVIIa) upon binding with TF forming the FVIIa/TF complex, which induces intracellular signaling pathways by activating protease activated receptor 2 (PAR-2). Upon subcutaneous administration, factor VIIa inhibitor PCI-27483 selectively inhibits factor FVIIa in the VIIa/TF complex, which may prevent PAR-2 activation and PAR2-mediated signal transduction pathways, thereby inhibiting tumor cell proliferation, angiogenesis, and metastasis of TF-overexpressing tumor cells. A phase I study in healthy volunteers was conducted to assess the PD and PK profiles of PCI- 27483 following a single, SC injection. The halflife of PCI-27483 was 10-12 h. The International Normalized Ratio (INR) was strongly correlated with drug plasma concentration. PCI-27483 was well tolerated. This compound has being evaluated in a phase Ib/II trial in patients with pancreatic cancer receiving treatment with gemcitabine. However, no recent development has been reported. The compound was originally developed by Celera, then licensed to Pharmacyclics (acquired by Abbvie in 2015) later. In 2012, the product was licensed to Novo Nordisk by Pharmacyclics for disease outside of oncology.

Gemilukast (ONO-6950) is an orally active compound that has been evaluated for the treatment of asthma. It is an CysLT1 and CysLT2 antagonist. Activation of CysLT2 receptors has been suggested to contribute to antigen-induced bronchoconstriction (constriction of the airways in the lungs) in certain asthma patients. In addition to its CysLT1 and CysLT2 antagonist activity, Gemilukast was shown to dose-dependently reduce LTC4-induced bronchoconstriction in asthmatic models, and reduce antigen-induced constriction of isolated human bronchi. A phase II trial with Gemilukast was discontinued in 2018.