Sepimostat (also known as FUT-187) was developed as a serine protease inhibitor including Clr, Cls, kallikrein, trypsin, plasmin, and thrombin. Sepimostat participated in early phase II clinical study on patients with reflux esophagitis. As a result, sepimostat could be used for postgastrectomy reflux esophagitis at the dose level of 300 mg/day or less. Experiments on rodents have shown that the drug could be also useful in the therapy of alcohol-induced pancreatitis. However, all these studies were discontinued.

Glenvastatin (HR780) is a synthetic HMG-CoA reductase (HMGCR) inhibitor. Like other statins, glenvastatin shows very low systemic bioavailability due to an extensive first pass effect at the intestinal and/or hepatic level. This is a positive trait, since the liver is the target organ for statins. Evidence has been found that glenvastatin protects the vascular endothelium from oxidant stress and inhibits the migration and proliferation of smooth muscle cells. In rabbits, long-term treatment with glenvastatin reduces the plasma cholesterol level, and decreases the liver cholesterol contents. There are no results of clinical trials for glenvastatin.

Tafluposide (also known as F 11782) is an epipodophyllotoxin derivative patented by Pierre Fabre Medicament as an antitumor agent. Tafluposide acts as a catalytic inhibitor of topoisomerases I and II, that capable of completely inhibiting the DNA-binding activity of topoisomerase. In preclinical models single or multiple i.p. doses of Tafluposide proves highly active against the s.c. grafted B16 melanoma, significantly increasing survival and inhibiting tumor growth. Tafluposide inhibits the number of pulmonary metastatic foci of the melanoma by 99%. In human tumor xenograft studies, multiple i.p. doses of Tafluposide results in major inhibitory activity against breast) tumors, as well as causing definite tumor regression. Significant activity was also recorded Tafluposide against the refractory lung xenografts.

Ulodesine (BCX4208) is a new, orally active, highly potent inhibitor of purine nucleoside phosphorylase (PNP) for the treatment of hyperuricemia and gout. Inhibition of PNP reduces the substrates available for XO to form uric acid. The drug is currently under development for the management of hyperuricemia in chronic gout. Two Phase II clinical trials have shown promising results regarding urate-lowering effect in both as monotherapy and in combination with allopurinol. Ulodesine shows no interaction with CYP450 isoforms and has no hepatic metabolism; therefore, no drug interactions were expected. Following the successful outcome of the Phase IIb clinical trial, Phase III development of ulodesine is planned. One concern regarding the use of ulodesine is its impact on T cells. Lack of PNP is associated with immunodeficiency and autoimmune disorders.

Ruboxistaurin is an orally bioavailable, selective, potent inhibitor of protein kinase C β developed for treating diabetic retinopathy. In vitro and in vivo non-clinical models have demonstrated that Ruboxistaurin decreases PKC β activity and ameliorates many of the effects of PKC β on pathologic processes in the retina. Ruboxistaurin prevents the slowing of retinal blood flow that is observed by fluorescein video angiography in the eyes of diabetic rats. It is also reported to cause regression of retinal neovascularization produced by laser-induced major branch vein occlusions in a porcine model. Ruboxistaurin positively affected the diabetes-induced retinal blood flow abnormalities in a Phase Ib study in diabetic patients. Ruboxistaurin is in phase III clinical trials for the treatment of diabetic nephropathy and diabetic macular edema. Eli Lilly had submitted Ruboxistaurin for approval in the US and the EU; however, the company subsequently discontinued development as it was unable to demonstrate sufficient efficacy

Varlitinib (Alternative Names: ARRY-334543; ARRY-543; ASLAN-001; Varlitinib tosylate) is a small molecule based reversible pan-HER inhibitor of EGFR, HER2 and HER4. In response to the binding of various ligands, these kinases undergo heterodimerisation and homodimerization, resulting in activation of numerous growth factor signaling pathways, by inhibiting the activation of the HER receptors via drug, effects such as shrinkage of the tumor and longer survival can be anticipated. In a large variety of cancers, the overexpression and/or constitutive activation of EGFR and HER2 are often observed and frequently correlate with poor clinical prognosis. Licensed from Array BioPharma with global rights for all indications, varlitinib is being developed as first-in-class drug for cholangiocarcinoma, gastric and colorectal cancer, and as best-in-class drug for breast cancer.

Rupintrivir is a peptide aldehyde that targets the human rhinovirus (HRV) 3C proteinase enzyme and has the potential for the treatment of the common cold. Rupintrivir is derived from AG-6084 - in order to develop human rhinovirus 3C protease inhibitors with improved pharmacological properties, Agouron replaced the backbone amide moiety of the series which yielded AG-6084, with a ketomethylene isostere. A phase II efficacy study has been completed in healthy patients infected with the rhinovirus. Ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. The fact that rupintrivir is active against noroviruses belonging to genogroup I (Norwalk virus), genogroup V (murine norovirus), and the recombinant 3C-like protease of a GII norovirus suggests that the drug exerts cross-genotypic anti-norovirus activity and will thus most likely be effective against the clinically relevant human norovirus strains. Rupintrivir is also a high affinity inhibitor of Enterovirus-71 3C protease.

Nestifylline [ABC 99] is a methylxanthine derivative that was at the preclinical stage of development with ABC for the treatment of asthma. ABC 99 has been studied in the animal to evaluate its pharmacological activity. This compound was found to have antibronchospastic activity in vitro and in vivo markedly greater than aminophylline. The new compound also had moderate antitussic properties and was an active mucoregulator. ABC 99 acts as an intestinal muscle relaxant, but it has no cardiovascular, urinary, or CNS side effects. The mechanism of ABC 99 could be explained by its inhibition of guinea-pig lung phosphodiesterases and affinity for adenosine receptors, particularly A2 receptors. ABC 99 was observed to have marked anti-inflammatory activity in a series of experimental trials involving the principal mediators of inflammation (PAF, histamine, serotonin, LTC4-like substances, etc). ABC 99 is of particular interest in the treatment of respiratory disorders involving obstructive inflammation and bronchial hypersensitivity.

TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Mubritinib displays > 4000-fold selectivity over other tyrosine kinases, such as EGFR, FGFR, PDGFR, Jak1, Src and Blk. A Phase I study to investigate a safe dose of Mubritinib, once daily (QD), in patients with tumors known to express HER2 (Breast Neoplasm, Pancreatic Neoplasm, Lung Neoplasm, Ovarian Neoplasm, Renal Neoplasm) has been completed, but appears to have been discontinued, as no new information on the drug has surfaced since December 2008.

Pimefylline is an N-methylated xanthine derivative. It is a coronary vasodilator and muscle relaxant.