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.

Vipadenant (V2006) is a small molecule, adenosine A2A receptor antagonist that was being investigated in Parkinson's disease. Due to safety concerns development ceased in 2010 and the rights were regained from Biogen Idec in 2011 with no further investment made. In October 2014, RedoxTherapies licensed Vipadenant as it has the potential to disrupt an immunosuppressive mechanism of tumour protection, generating improved efficacy for immunotherapies of certain cancers when used in combination with other drugs.

Bimosiamose, discovered by Encysive Pharmaceutical and presently being developed by Revotar Biopharmaceuticals, is an 863 g/mol molecular weight dimer with minimal carbohydrate content and is, to date, the leading selectin inhibitor in clinical development. It was developed as anti-inflammatory drug fir the treatment of acute chronic inflammatory disorders including COPD. This compound has shown promise in a phase IIa 'proof of concept' trial in patients with asthma, reducing airway recruitment of eosinophils after intravenous administration. In acute lung injury, neutrophils (a type of white blood cells, thus belonging to the group of cells of the body’s defence system-the immune system) are drawn to the small lung bloodvessels and migrate into the air sacs (alveoli). There they release substances, which cause the inflammation leading to further destruction of the lung tissue. Bimosiamose disodium is expected to hinder the migration of these neutrophils into the alveoli.

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.

Hydroxyflutamide is the major active metabolite of flutamide. Flutamide undergoes extensive first-pass metabolism by CYP1A2 to its metabolite hydroxyflutamide and its hydrolysis product, 3-trifluoromethyl-4-nitroaniline. Hydroxyflutamide is a more powerful antiandrogen in vivo, with higher affinity for the receptor than that of flutamide. Hydroxyflutamide is in phase II clinical trials for the treatment of prostate cancer. However, a drug resistance problem appears after about one year's treatment. Per-residue free energy decomposition analyses indicate that N705, T877, and M895 androgen receptor mutations are vital residues in the agonist/antagonist mechanism of hydroxyflutamide.

Flurocitabine is an anti-metabolite that was developed by Hoffmann-La Roche for the treatment of cancer. The drug is metabolized to 2 biologically active substances, AFC (1-beta-D-arabinofuranosyl-5-fluorocytosine) and AFU (arabinofuranosyl-5-fluorouracil). Flurocitabine was tested against stomach cancer, pancreatic cancer, small cell lung cancer and AML, however, the development was terminated in the early phases.

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.

AstraZeneca (formerly Astra) is developing robalzotan (NAD-299, AZD-7371), a 5-HT1A antagonist, for the potential treatment of depression and anxiety. The compound has entered phase II trials but was discontinued. Then it investigated for the treatment of irritable bowel syndrome, but the study was prematurely terminated. The same final has expected the development of robalzotan in phase II to treat overactive bladder, this investigation was terminated in July 2005.

Sonolisib (PX-866) is a small-molecule inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. Sonolisib inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Inhibition of the PI3K pathway with Sonolisib leads to inhibition of cell growth and decreased activation of downstream targets in GBM, both in vitro and in vivo, using U87–tumor-bearing mice, including Akt, S6, and mTOR. Sonolisib was in phase II clinical trials by Oncothyreon for the treatment of glioblastoma multiforme and castration-resistant prostate cancer (CRPC). It was in phase I/II clinical trials for the treatment of malignant melanoma, non-small cell lung cancer and Head and neck cancer. In clinical trials, Sonolisib was well tolerated, with common side effects being diarrhea, nausea, vomiting, and elevated liver enzymes. However, no recent development has been reported.