Veliparib (ABT-888) is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier, and potentiates temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. AbbVie is developing veliparib for the treatment of cancers. Clinical trials are underway worldwide, investigating veliparib primarily as part of a combination therapy in oncology indications such as brain, colorectal, melanoma, ovarian, prostate and pancreatic cancers.

Banoxantrone (formally known as AQ4N), a bioreductive drug that is irreversibly converted to AQ4, a stable DNA affinic cytotoxic compound. Banoxantrone is activated by haem-containing reductases such as inducible nitric oxide synthase (iNOS). In hypoxic cells, AQ4N is reduced to the topoisomerase II inhibitor AQ4. By inhibition of topoisomerase II within these hypoxic areas, AQ4N has been shown to sensitize tumors to existing chemo- and radiotherapy treatments. Novacea, the company which was responsible for clinical trials for banoxantrone had decided to scale back on its clinical development, including discontinuing the clinical trial in acute lymphoblastic leukemia and delaying the planned clinical trial in B-cell lymphoma. The company decided to continue enrollment in an ongoing Phase 1b/2a clinical trial in patients with glioblastoma multiforme. However, further information about these clinical trials are not available. Some recent experiments have shown that targeting hypoxic tumors with high levels of iNOS with a combination of AQ4N and radiotherapy could be a useful clinical therapeutic strategy.

Indotecan (LMP400) is a novel indenoisoquinoline derivative with specific topoisomerase I inhibition activity, developed by Division of Cancer Treatment and Diagnosis National Cancer Institute for cancer treatment. In preclinical studied Indotecan inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. Low doses of Indotecan decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. In vitro, Indotecan showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. Recently Indotecan has entered Phase I clinical trials for the treatment of cancer patients at the National Cancer Institute, and definite plans are being formulated to commence Phase II clinical trials.

Bafetinib (NS-187, INNO-406) is a second-generation tyrosine kinase inhibitor in development by CytRx under license from Nippon Shinyaku for treating Bcr-Abl+ leukemia's, including chronic myelogenous leukemia (CML) and Philadelphia+ acute lymphoblastic leukemia. It is a rationally developed tyrosine kinase inhibitor based on the chemical structure of imatinib, with modifications added to improve binding and potency against Bcr-Abl kinase. Besides Abl, bafetinib targets the Src family kinase Lyn, which has been associated with resistance to imatinib in CML. In preclinical studies, bafetinib was 25- to 55-fold more potent than imatinib in vitro and ≥ 10-fold more potent in vivo. Bafetinibinhibits 12 of the 13 most frequent imatinib-resistant Bcr-Abl point mutations, but not a Thr315Ile mutation. A small fraction of bafetinib crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. Data from a phase I clinical trial conducted in patients with imatinib-resistant or -intolerant CML have confirmed that bafetinib has clinical activity in this setting, inducing a major cytogenetic response in 19% of those patients in chronic phase. Currently, bafetinib is being developed in two phase II clinical trials for patients with B-cell chronic lymphocytic leukemia and prostate cancer, and a trial is in progress for patients with brain tumors. In 2005, the compound was licensed to Innovive Pharmaceuticals (acquired by CytRx Oncology in 2008) by Nippon Shinyaku on a worldwide basis, with the exception of Japan, for the treatment of CML. Orphan drug designation was assigned to the compound for the treatment of CML in the U.S in 2007 and in the E.U. in 2010. Bafetinib is in phase II for the treatment of hormone-refractory prostate cancer and chronic lymphocytic leukemia.

Quiflapon Sodium (MK-0591; (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) had been in phase II clinical studies for the treatment of inflammatory bowel disease, but the study was discontinued later, because in spite of MK-591 markedly inhibited Leukotrienes (LT) biosynthesis, it did not differ significantly from placebo in clinical efficacy. Also was discovered, that MK-0591 may modify the airway changes associated with bronchial hyper responsiveness, as well as offer symptomatic relief in asthma. MK-0591 is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor with an IC50 value of 1.6 nM in a FLAP binding assay. In additional, recently was discovered, that MK591 possesses all major attributes of a standard anti-metastatic agent with significant cancer-selective effect, and suggest that MK591 may turn out to be an effective agent for therapy of castration-resistant, bone-metastatic prostate cancer. Though details of the molecular underpinnings of the anti-metastatic action of MK591 are unknown at this time, this finding gives an opportunity for further exploration to better understand the signaling mechanisms involved by in vitro and in vivo experiments.

ITAZIGREL, a thiazole derivative, is a potent platelet aggregation inhibitor.

Hycanthone is a thioxanthene derivative of lucanthone with anti-schistosomal activity and potential antineoplastic activity. It was clinically available for the treatment of human schistosomiasis. Anti-helmintic action relies on its ability to inhibit worm monoamine oxidase and cholinesterases. Hycanthone produced immediate side effects such as hepatotoxicity and gastrointestinal disturbances, and was consequently withdrawn. Hycanthone inhibits apurinic endonuclease-1 (APE1) by direct protein binding. Hycanthone was used in the 1980s as antitumor agents, it was pulled out of Phase II trials.

Ombrabulin is an experimental drug candidate discovered by Ajinomoto and further developed by Sanofi-Aventis for cancer treatment. Ombrabulin is a synthetic water-soluble analog of combretastatin A4, derived from the South African willow bush (Combretum caffrum), with potential vascular-disrupting and antineoplastic activities. Ombrabulin binds to the colchicine binding site of endothelial cell tubulin, inhibiting tubulin polymerization and inducing mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their substrate, tumor blood vessels collapse; the acute disruption of tumor blood flow may result in tumor necrosis. Ombrabulin has been used in trials studying the treatment of Sarcoma, Neoplasms, Solid Tumor, Neoplasms, Malignant, and Advanced Solid Tumors, among others. In January 2013, Sanofi said it discontinued development of Ombrabulin after disappointing results from phase III clinical trials.

Rostafuroxin (PST 2238) is a digitoxygenin derivative, which selectively displaces ouabain from the Na ,K -ATPase receptor. PST 2238, at concentrations up to 10−4 M, did not show any significant interaction with a- and b-adrenergic, D1, D2, D3, 5-HT1, 5-HT2, H1, H2, M1, M2, A1, A2, Ca2 , Na , or K channel–associated receptors, AT1, AT2, ETa, ETb, GABA, thromboxane, vasopressin, angiotensin II, or the steorid-hormone receptors (androgen, progestogen, estrogen and mineralocorticoid), confirming that PST 2238 is specific for Na ,K -ATPase. Rostafuroxin has been developed in an attempt to unravel the contribution of mutated adducin and endogenous ouabain in the pathogenesis of hypertension. The compound lowered blood pressure in Milan hypertensive rats and humans. Rostafuroxine had been in phase II clinical trials for the treatment of hypertension. Following adverse events in Rostafuroxin group were described: dizziness, headache, upper respiratory tract infections, high blood pressure.

Talarozole (formerly R115866) is a new highly potent and selective azole derivative, which inhibits cytochrome-P450-dependent all-trans-retinoic acid catabolism by blocking the cytochrome P450 enzyme isoform CYP26, a retinoic acid hydroxylase. It is in clinical development for the treatment of psoriasis and acne. However, no local pharmacokinetic data on the diffusion behaviour of talarozole in the skin itself are available. As topical application might be an interesting alternative to oral therapy because of the reduced systemic side effects. The distribution of talarozole within the skin was investigated: 80% was located in the epidermis, while the remaining 20% was found in the dermis. The epidermal concentration of talarozole achieved after a single topical application was sufficiently high to enable the potential induction of local retinoid-like effects.