Bardoxolone methyl, the C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) known as CDDO-Me or RTA 402, is one of the derivatives of synthetic triterpenoids. Bardoxolone methyl directly blocks IKKbeta activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the IKKbeta activation loop. Binding of bardoxolone methyl to Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) disrupts its critical cysteine residues, leading to the release of the nuclear factor erythroid 2-related factor 2 (Nrf2), which hinders its ubiquitination and finally leads to its stabilization and nuclear translocation. In the nucleus, Nrf2 activates the transcription of phase 2 response genes, leading to a coordinated antioxidant and anti-inflammatory response. In addition, it acts as an antagonist of the peroxisome proliferator-activated receptor gamma. Through Keap1/Nrf2 and nuclear factor-κB pathways, this agent can modulate the activities of a number of important proteins that regulate inflammation, redox balance, cell proliferation and programmed cell death. This agent is generally well tolerated, but it may increase adverse cardiovascular events. Presently, it is being further tested for the treatment of patients with chronic kidney disease, cancer, and pulmonary arterial hypertension.

Brivanib is a pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. It specifically targets and strongly binds to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis. Brivanib has a moderate potency compared to VEGFR-2 against VEGFR-1 and FGFR-1 as well. Brivanib is suggested to be efficient in treatment of hepatocellular carcinoma (HCC). As first-line and as second-line therapy brivanib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC in phase II clinical trials. On 3 march 2011, orphan designation was granted by the European Commission to Bristol-Myers Squibb for brivanib alaninate for the treatment of hepatocellular carcinoma.[

Odanacatib is a potent, selective, and neutral cathepsin K inhibitor, an enzyme involved in bone resorption. Merck & Co was developing odanacatib, a once-weekly, oral Odanacatib, for the treatment of postmenopausal osteoporosis and osteoporosis in men. Merck & Co. has discontinued development of its cathepsin K inhibitor odanacatib, citing an increased risk of cardiovascular events for the osteoporosis drug.

Entinostat (MS-275) is an orally active, highly selective, small-molecule histone deacetylase inhibitor (HDACi) derived from benzamide. Entinostat preferentially inhibited HDAC1 versus HDAC3 and had no inhibitory activity toward HDAC8. The time to maximum plasma concentration (tmax) of entinostat ranged from 0.5 to 60h (median of 2h). Elimination of the drug was bi-exponential, with a terminal half-life of 30-80h. Entinostat is a well-tolerated that demonstrates promising therapeutic potential in both solid and hematologic malignancies. Its efficacy does not appear directly dose-related, and as such, more relevant biomarkers are needed to adequately assess its activity.

Calcimycin is an ionophore, polyether antibiotic from Streptomyces chartreusensis. It binds and transports calcium and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems. Calcimycin has antibiotic properties against gram-positive bacteria and fungi. Inex Pharmaceuticals Corporation (Canada) reported an innovative application of Calcimycin. "Inex" used Calcimycin as a molecular tool in order to make artificial liposomes loaded with anti-cancer drugs such as Topotecan. In in vitro fertilization (IVF) field, Ca Ionophore can be used in case of low fertilization rate after ICSI procedure, particularly with Globozoospermia (Round Head sperm syndrome), Ca Ionophore plays role in oocyte activation after ICSI. Recommended use is 0.5 microgram/ml twice for 10 min interrupted with fresh media with 30 min incubation, followed with regular injected eggs culture for IVF

DOV 216,303 [(+/-)-1-(3, 4-dichlorophenyl)-3-azabicyclo-[3.1.0] hexane hydrochloride] is the prototype of a class of compounds referred to as "triple" reuptake inhibitors. DOV 216,303 were licensed from Wyeth in 1998. This compound inhibits the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely linked to major depressive disorder. In August 2004, DOV entered into a development and commercialization partnership for the triple reuptake inhibitors (DOV 21,947 and DOV 216,303) with Merck for depression.

Senicapoc (ICA-17043) is a blocker of Gardos channel, a calcium-activated potassium channel, in the red blood cell. Preclinical studies and studies in transgenic models of Sickle cell disease (SCD) show that inhibition of potassium efflux through the Gardos channel is associated with an increased haemoglobin level, decreased dense cells and decreased hemolysis. Senicapoc is well tolerated when administered to SCD patients and produces dose-dependent increases in hemoglobin and decreases in markers of hemolysis. Senicapoc exerts anti-fibrotic and anti-inflammatory activities. Senicapoc has previously been in Phase III and Phase II clinical trials for the treatment of SCD and asthma, respectively.

NMED-160 (also known as MK-6721, NP-118809, Z-160) is a potent N-type calcium channel blockers, which has good selectivity over L-type calcium channels. Neuromed Pharmaceuticals developed this compound for the treatment of the chronic pain. However, that study was discontinued in 2007 in spite of absence of adverse events, but because drug did not demonstrate the ideal, pharmaceutical characteristics considered necessary to advance the compound further in development. Then Zalicus, Inc. was developing that drug for the treatment of chronic neuropathic pain associated with lumbosacral radiculopathy and post-herpetic neuralgia and drug was in the phase II clinical trial. Nevertheless, based on the result from trials, where Z160 did not meet the primary endpoint, Zalicus was also discontinuing the Z160 program.

BMS-582949 acts as a dual action kinase inhibitor. It inhibits both p38 mitogen-activated protein kinase (p38 MAPK) activity and activation of p38. As a blocking agent for activation of p38 kinase BMS-582949 appeared to be well suited to resist such cellular responses that would drive p38 activation more strongly. BMS-582949 is in Phase II clinical trials for the treatment of rheumatoid arthritis, psoriasis, and atherosclerosis.

Rabusertib is a Chk1 kinase inhibitor which was developed by ICOS for the treatment of cancer. The drug was tested in phase II of clinical trials for pancreatic cancer and non small cell lung carcinoma, but its development was discontinued. Now the drug is undergoing phase I trial in Japanese patients with solid tumors.