Aloxistatin (E64d) is an irreversible and membrane-permeable cysteine protease inhibitor. Aloxistatin was developed for treating muscular dystrophy. Open trials on 73 Duchene’s muscular dystrophy patients were conducted for 3 years at four Japanese national sanatoriums and resulted in some muscle strength improvement but the results were inconclusive and final double-blind studies did not confirm the results. Taisho has discontinued development of aloxistatin for the potential treatment of muscular dystrophy. The  trials completed through Phase 3. In animal models Aloxistatin (100 mg/kg, p.o.) strongly inhibits the cathepsin B&L activities in the skeletal muscle, heart and liver of hamsters. In spinal cord injury (SCI) rats, Aloxistatin provides neuroprotection in SCI lesion and penumbra.Aloxistatin reduces brain amyloid-β and improves memory deficits in Alzheimer's disease animal models by inhibiting cathepsin B activity.

The new chemical entity KC12615 is a potent f neutral endopeptidase inhibitor with additional endothelin-converting enzyme (ECE)–inhibitory activity.2 KC12615 is the hydrolyzed form of the oral prodrug SLV306 (daglutril). In plasma, the compound increases natriuretic peptide levels and prevents the formation of endothelin-1 by inhibiting the degradation of its precursor, big endothelin. It is investigated for use/treatment in congestive heart failure and hypertension.

Methoxyamine (TRC102) is an orally bioavailable small molecule with potential adjuvant activity, that may potentiate the antitumor activity of alkylating agents. Methoxyamine covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER) that causes topoisomerase II-dependent irreversible strand breaks and apoptosis. Methoxyamine is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute or Case Comprehensive Cancer Center.

Nesbuvir (previously known as VB-19796 and HCV-796) is an inhibitor of hepatitis C NS5B RNA-dependent RNA polymerase. The drug was tested in phase II in patients with hepatitis C in combination with rebetol and peg-intron, however, its development was terminated due to safety issues.

Romazarit, (Ro 31-3948, 7), 2-[[2-(4-chlorophenyl)-4-methyl-5-oxazolyl]methoxy]-2-methylpropionic acid is a substituted heterocyclic alkoxypropionic acid. Romazarit was considered to be a potential disease-modifying antirheumatic drug. Romazarit was withdrawn due to its toxicity profile.

Esreboxetine (PNU-165442G) is the (S,S)-(+)-enantiomer of antidepressant reboxetine, a selective norepinephrine reuptake inhibitor. The (S,S)-enantiomer is a more potent inhibitor of norepinephrine transporter than (R,R)-enantiomer. Esreboxetine was being developed by Pfizer, primarily for the treatment of fibromyalgia.

Semagacestat (LY-450139) was a gamma secretase inhibitor being developed as a treatment for Alzheimer's disease by Eli Lilly. It was hoped that the drug would help to delay the onset of severe Alzheimer's disease, and thereby help preserve cognitive and executive functioning and in turn improve patient quality of life. Semagacestat (LY-450139) is designed to inhibit gamma secretase, an enzyme that is involved in the cleavage of APP to beta-amyloid. By decreasing production of beta-amyloid, it is hoped that gamma secretase inhibitors will exert a disease-modifying effect in Alzheimer's disease and thus slow or halt the destruction of nerve cells – the final stage in the amyloid cascade hypothesis. In March 2008 semagacestat (LY-450139) advanced to Phase III development, where it was evaluated in the IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) trial, the first Phase III trial for this new anti-dementia drug. In August 2010, Eli Lilly announced its decision to halt the development of Semagacestat. The decision was taken after analysing the preliminary results of the second Phase III clinical trial of the drug, which indicated that semagacestat failed to slow disease progression. The drug, in fact, worsened cognition and the ability to perform day-to-day activities.

Motapizone is a pyridazinone derivative patented by pharmaceutical company Nattermann, A., und Cie. G.m.b.H. as an antithrombotic and hypotensive agent. Motapizone ats as a potent inhibitor of the isoenzyme phophodiesterase type III. In preclinical studies potent antithrombotic and hypotensive properties of motapizone has been shown in rats, cats, and dogs. In normal human volunteers, single oral doses of motapizone up to 10 mg produced significant inhibition of platelet aggregation measured by the ex vivo method. These effects were dependent upon the dose of motapizone and associated with an increase in heart rate and a reduction in diastolic blood pressure.

Tivantinib (ARQ 197) is the first non-ATP-competitive small molecule that selectively targets the c-Met receptor tyrosine kinase. Exposure to Tivantinib resulted in the inhibition of proliferation of c-Met-expressing cancer cell lines as well as the induction of caspase-dependent apoptosis in cell lines with constitutive c-Met activity. ArQule and its collaborators Daiichi Sankyo and Kyowa Hakko Kirin are developing tivantinib as a potential therapy for many cancers. c-Met is overexpressed in many cancers. Tivantinib currently is in phase 3 clinical development for the treatment of hepatocellular carcinoma and non-small cell lung cancer.