Fazarabine (Arabinofuranosyl-5-azacytosine) is a synthetic pyrimidine nucleoside which combines the arabinose sugar of cytosine arabinoside with the triazine base of 5-azacytidine. It has demonstrated activity against a variety of human solid tumor xenografts including colon, lung and breast cancers. It has been selected by the Division of Cancer Treatment, National Cancer Institute for clinical development as an antineoplastic agent based on its high degree of activity against a broad range of tumor types in preclinical studies. Therapeutic activity has been observed against murine and human leukemias, transplantable murine solid tumors, and human tumor xenografts. Arabinosyl-5-azacytosine exhibited a broader spectrum of activity against human solid tumors than cytosine arabinoside. The mode of action of fazarabine is mediated through its incorporation into DNA and inhibition of DNA synthesis.

Ibiglustat (GZ/SAR402671 or Genz-682452) is a small molecule inhibitor of glucosylceramide synthase. Ibiglustat has been demonstrated to effectively lower glycosphingolipid synthesis. Genzyme, a Sanofi Company is developing Ibiglustat for the treatment of Parkinson's Disease, Gaucher Disease, and Fabry Disease.

Saracatinib (AZD0530) is an oral, dual inhibitor of c-Src/Abl kinases initially developed by AstraZeneca for the treatment of cancer. The drug was tested for many neoplasms and reached phase III for ovarian cancer (in combination with paclitaxel), however without demonstrating any significant effect. Sarcatinib is also tested in patients with Alzheimer's Disease (Phase II). Its effect on Alzheimer's Disease patients is explained by inhibition of another kinase, Fyn, which is highly expressed in brain.

AST-1306, also known as Allitinib, is an orally active potent, selective, irreversible inhibitor of the HER family of receptor tyrosine kinases. AST-1306 inhibits the enzymatic activities of wild-type epidermal growth factor receptor (EGFR) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu) transgenic breast cancer mouse models. Allitinib is in Phase I clinical trial for the treatment of advanced solid tumors. Serious adverse effects detected were: diarrhea, dehydration and hyperbilirubinemia.

Alvocidib (also known as Flavopiridol or HMR-1275) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development for the treatment of acute myeloid leukemia, by Tolero Pharmaceuticals, Inc. As a broad spectrum CDK inhibitor, Alvocidib can inhibit cell cycle progression in either G1 or G2 and induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. Alvocidib exhibits potent cytotoxicity against a wide variety of tumor cell lines (LNCAP, HCT116, A2780, K562, PC3, and Mia PaCa-2) with IC50 values ranging from 16 nM for LNCAP to 130 nM for K562. Administration of Alvocidib at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, and active against the human A2780 ovarian carcinoma implanted sc in nude mice). Alvocidib treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. Tolero Pharmaceuticals Inc. announced that the FDA has granted orphan drug designation for Alvocidib, its cyclin-dependent kinase small molecule inhibitor, for the treatment of patients with acute myeloid leukemia.

Firategrast (SB683699) is an orally bioavailable alpha4 beta1/alpha4 beta7 integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS), that had been studied in phase II trials at GlaxoSmithKline under a license from Mitsubishi Tanabe Pharma for the oral treatment of multiple sclerosis (MS) in Europe. GlaxoSmithKline and Tanabe Seiyaku (now Mitsubishi Tanabe Pharma) had been studying the drug candidate for the treatment of asthma, rheumatoid arthritis (RA) and Crohn’s disease, but these studies had being discontinued. Firategrast is a drug for the treatment of multiple sclerosis (MS) which is found to be caused by the migration of leucocytes (such as monocytes, T cells, B cells and dendritic cells) into CNS. And the integrin α4β1 is found to take participate in the migration through activating the leucocytes. Firategrast has a much shorter half-life than natalizumab with about 2.5 hours to 4.5 hours. It is found to inhibit the binding of the integrins to the associated ligands, including vascular cell adhesion protein 1 and mucosal addressin cell adhesion molecule 1. In CNS, firategrast treatment caused moderate decreases of total lymphocyte count, lymphocyte subset count and the ratio of CD4 to CD8. In peripheral blood, firategrast treatment resulted in the increases of total lymphocyte count, all lymphocyte subset count as well as the peripheral CD34+ early haematopoietic progenitor cell count. Firategrast was well tolerated at the maximum doses of 1200 mg for men and 900 mg for women. Firategrast showed no side effects, such as PML or JC-virus reactivation, at these doses. In Phase I clinical trials, the administration of firategrast significantly reduced the cumulative number of new gadolinium-enhancing lesions in patients with relapsing remitting MS.

Ataciguat is a novel anthranilic acid derivative that belongs to a new structural class of sGC activators which are capable of activating the oxidized form of sGC. Ataciguat, a nitric oxide-independent soluble guanylate cyclase activator, is being developed by Sanofi (previously sanofi-aventis), in collaboration with Mayo Clinic and National Center for Advancing Translational Sciences. Ataciguat is in phase II clinical trials for the treatment of aortic valve stenosis. It had been used to treat neuropathic pain and peripheral arterial disease, but this research has been discontinued.

Poziotinib is an inhibitor of EGFR tyrosine kinase family. The drug is being tested in phase II of clinical trials for different cancers: breast cancer, lung adenocarcinoma, head and neck squamous cell carcinoma, HER-2 positive advanced gastric cancer (in combination with Paclitaxel and Trastuzumab).

Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU) is a thymidine nucleoside analog with activity against various herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. Herpes virus thymidine kinase considered to be a target of FIAU. In a Phase II study, fialuridine induced a severe toxic reaction in chronic hepatitis B patients characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. These clinical manifestations led to the hypothesis that the toxicity of FIAU was mediated through mitochondrial dysfunction, possibly as a result of the inhibition of mitochondrial DNA polymerase gamma and/or incorporation of FIAU into mitochondrial DNA.

AZD-6482 is being developed by AstraZeneca to evaluate its therapeutic effects in the treatment of thrombosis. AZD-6482 is essentially a PI3K-beta inhibitor. It is a PI3Kβ inhibitor with IC50 of 10 nM, 8-, 87- and 109-fold more selective to PI3Kβ than PI3Kδ, PI3Kα and PI3Kγ in cell-free assays. by targeting PI3Kβ, AZD-6482 specifically inhibits thrombosis without interfering with normal haemostasis. Therefore, AZD-6482 is used as an anti-thrombotic drug for the prophylaxis of thrombotic disorders. AZD-6482 was in phase I trials by AstraZeneca for the prevention of thrombosis. However, the study was discontinued.