Emricasan (IDN- 6556 or PF-03491390) (3-[2-[(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid) is a pan-caspase inhibitor. Testing in vitro enzyme assays demonstrated that emricasan efficiently inhibits all human caspases at low nanomolar concentrations. Preclinically, emricasan was effective in inhibiting apoptosis of sinusoidal endothelial cells. Emricasan has marked efficacy in models of liver disease after oral administration and thus, is an excellent candidate for the treatment of liver diseases characterized by excessive apoptosis. This drug is a first-in-class anti-apoptotic caspase inhibitor with demonstrated preliminary efficacy in liver-impaired patients in humans.

Netobimin is a carbamate compound which is used as an anthelmintic drug in veterinarymedicine. Netobimin-containing products are available as liquid suspensions which are intendedfor oral administration. Products are available for sheep and cattle. An oral dose of 7.5 mg/kg bw is recommended for the treatment of gastrointestinal infestations of roundworms and tapeworms;and 20 mg/kg bw is recommended for type II ostertagiasis and adult flukes. In order to be pharmacologically active, netobimin needs to be converted to the broad spectrumanthelmintic drug albendazole, by the splitting off of a side-chain and the formation of abenzimidazole group. This occurs naturally in the ruminant gut.

Zaurategrast (CDP323) is an ethyl ester prodrug of CT7758, a potent carboxylic acid antagonist of integrin alpha4-beta1 (α4β1) or very late antigen 4 (VLA4). CDP323 was under development with UCB and Biogen Idec for the treatment of multiple sclerosis. Its development was discontinued in 2009 based on inadequate interim efficacy data in a phase II clinical trial.

Imiglitazar (also known as TAK-559) is a dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist patented by Japanese pharmaceutical company Takeda Chemical Industries for the prevention or treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance, and impaired glucose tolerance. Imiglitazar shows potent hypoglycemic and hypolipidemic activity and has been studied in clinical trials in treating subjects receiving a stable dose of insulin to control type 2 diabetes mellitus. Unfortunately, Imiglitazar shows hepatotoxicity and has never been marketed.

Traxoprodil (CP-101,606) is a potent, selective N-Methyl-D-aspartate (NMDA) receptor (NR2B subunit) antagonist under development by Pfizer for its potential as a neuroprotectant in head injury and neurodegenerative disease. It is in phase II trials in the US and in phase I in Japan for the potential treatment of head injury, such as, Depressive Disorder, Major and Parkinson's Disease. CP-101,606 does not protect against glutamate-induced neurotoxicity in cultured cerebellar neurons, up to a dose of 10 uM. These results are consistent with CP-101,606 being a potent NMDA antagonist, selective for the type of NMDA receptor associated with the hippocampus. Some further investigation revealed that CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.

Tozasertib, originally developed as VX-680 by Vertex (Cambridge, MA) and later renamed MK-0457 by Merck (Whitehouse Station, NY), was the first aurora kinase inhibitor to be tested in clinical trials. The drug, a pyrimidine derivative, has affinity for all aurora family members at nanomolar concentrations with inhibitory constant values (Ki(app)) of 0.6, 18, and 4.6 nM for aurora A, aurora B, and aurora C, respectively. Preclinical studies confirmed that tozasertib inhibited both aurora A and aurora B kinase activity, and activity has been reported against prostate, thyroid, ovarian, and oral squamous cancer cell lines. Upon treatment with tozasertib, cells accumulate with a 4N DNA content due to a failure of cytokinesis. This ultimately leads to apoptosis, preferentially in cells with a compromised p53 function. Tozasertib is an anticancer chemotherapeutic pan-aurora kinase (AurK) inhibitor that also inhibits FMS-like tyrosine kinase 3 (FLT3) and Abl. Tozasertib is currently in clinical trials as a potential treatment for acute lymphoblastic leukemia (ALL). In cellular models of cancer, tozasertib activates caspase-3 and PARP and decreases expression of HDAC, increasing apoptosis and inhibiting cell growth. In other cellular models, tozasertib inhibits cell proliferation and metastasis by blocking downstream ERK signaling and downregulating cdc25c and cyclin B. This compound also decreases tumor growth in an in vivo model of prostate cancer.