Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. It also inhibits several cancer related tyrosine kinases as well as Abl, Trk-a, fibroblast growth receptor-1 and Ret. Danusertib is in phase II trials for the treatment of solid tumours, prostate cancer and chronic myeloid leukemia (CML). The most frequently reported side effects were neutropenia, nausea, anorexia, fatigue, and diarrhea.

Refametinib (RDEA-119, BAY- 869766) is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK1/2) activity, Refametinib binds to an allosteric pocket adjacent to the ATP binding site, locking the enzyme in a catalytically inactive conformation. This compound is highly efficacious at inhibiting cell proliferation in several tumor cell lines in vitro. In vivo, Refametinib exhibits potent activity in xenograft models of cancers. Ardea Biosciences (a subsidiary of AstraZeneca) and Bayer HealthCare are developing refametinib for the treatment of cancer. The sulfonamide agent was originally developed by Valeant Pharmaceuticals International. Refametinib is in phase II development for hepatocellular carcinoma, and phase I/II development for pancreatic cancer and other solid tumours.

Ralimetinib (LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 mitogen-activated protein kinase. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non-small cell lung cancer, ovarian, glioma, myeloma, breast). Eli Lilly is developing ralimetinib for the treatment of cancer.

Stannsoporfin is a mesoporphyrin derivative patented by Rockefeller University as competitive heme oxygenase (HO) inhibitor for the prevention of hyperbilirubinemia in infants at risk of developing jaundice. Parenteral administration of Stannsoporfin has been shown to suppress or moderate jaundice in a wide variety of experimental and naturally occurring forms of hyperbilirubinemia in animals and man. Stannsoporfin is rapidly cleared from the plasma in animals, in adult humans, and in newborn infants and may inhibit competitive heme oxygenase for prolonged periods. The Stannsoporfin decreases the production of carbon monoxide from heme and increases the biliary excretion of unmetabolized heme but has no effect on the metabolic disposition of preformed bilirubin.

LADOSTIGIL, a rasagiline derivative, is a reversible acetylcholinesterase and butyrylcholinesterase inhibitor with neuroprotective properties. It also acts as an irreversible brain monoamine oxidases inhibitor. It is under development for the treatment of neurodegenerative disorders like dementia and Alzheimer's disease.

Dacinostat (also known as LAQ824), is a hydroxamate histone deacetylase inhibitor with potential anticancer activity. Dacinostat inhibits histone deacetylase enzymatic activities in vitro and transcriptionally activated the p21 promoter in reporter gene assays. Tumor cells treated with Dacinostat caused acetylation of HSP90 and degradation of its cargo oncoproteins. Flow cytometry studies revealed that both tumor cell lines and normal diploid fibroblasts arrested in the G2/M phase of the cell cycle after Dacinostat treatment. However, an increased sub-G1 population at 48 h (reminiscent of apoptotic cells) was only observed in the cancer cell lines treated with Dacinostat. Dacinostat exhibited antitumor effects in a xenograft animal models. In phase I trials, Dacinostat was well tolerated at doses that induced accumulation of histone acetylation, with higher doses inducing changes consistent with HSP90 inhibition. In another phase 1 in patients with advanced solid tumors, grade 3 or 4 toxicities were observed. Dacinostat had been in phase II clinical trials by Novartis for the treatment of solid tumors but further studies were discontinued.

Evobrutinib is a highly selective, irreversible inhibitor of Bruton's tyrosine kinase (BTK). It potently inhibits BCR- and Fc receptor-mediated signaling and, thus, subsequent activation and function of B cells and innate immune cells such as monocytes and basophils. Evobrutinib demonstrated effectivity in autoimmune disease preclinical models. Evobrutinib is being developed by Merck Serono for the treatment of various autoimmune disorders.

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.

Setileuton [MK-0633] is a selective inhibitor of the 5-lipoxygenase enzyme, which was under investigation for the treatment of asthma and atherosclerosis. Setileuton has been in phase II clinical trials by Merck Sharp & Dohme for the treatment of asthma, chronic obstructive pulmonary disease (COPD) and atherosclerosis. However, this research has been discontinued.

Adibendan [BM 14478] is a phosphodiesterase inhibitor that increases the calcium sensitivity of the myocardium. Adibendan selectively inhibited phosphodiesterase III (PDE III) activity concentration-dependently (IC50 = 2.0 umol/l). The IC50 values for the inhibition of PDE I or II were more than 60-fold higher. Adibendan has both vasodilator and positive inotropic properties. Adibendan was investigated as the potential treatment of heart failure and ischaemic heart disorders. However, research has been discontinued at phase II of development.