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.

Vinzolidine (also known as LY104208), a semisynthetic vinblastine derivative that was developed as an antitumor agent. Vinzolidine participated in clinical trials phase II in the oral formulation in patients with lymphoma, particularly Hodgkin's disease. In addition, it was studied in patients with Kaposi's sarcoma, non-small cell lung cancer, colorectal cancer, and breast cancer. It was found significant side effects included neurotoxicity and dose-related myelosuppression. As a result, was suggested intravenous route of administration for vinzolidine could be more safely. However, the phase I trial of intravenous vinzolidine was shown no antitumor activity. The further development of this drug was discontinued.

Vinepidine, a derivative of vincristine participated in clinical trials as an antineoplastic agent. As a result, the extreme neuromuscular toxicity was observed, that is why this study was discontinued.

Indibulin is a novel synthetic compound that was identified in a cell-based screening assay to discover cytotoxic drugs. Indibulin destabilizes microtubules and blocks cell cycle transition specifically at the G2-M phase. Indibulin effectively induces apoptosis through Bcl-2 phosphorylation and Bax translocation in human malignant glioma cells in a p53-independent manner. This agent has been shown to be active against multidrug-resistant (MDR) and taxane-resistant tumour cell lines. Indibulin was used in phase I/II clinical trials of patients with advanced solid tumours (metastatic breast cancer). Pharmacokinetic analysis showed a better tolerability underfeeding condition. Dose-limiting toxicities were nausea and vomiting, which seemed to be related to solvent lactic acid.

Ispinesib (SB-715992) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP). KSP, also known as HsEg5, is a kinesin that plays an essential role in the formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. Ispinesib is the highly specific small-molecule inhibitor of KSP tested for the treatment of human disease. It causes mitotic arrest and growth inhibition in several human tumor cell lines and is currently being tested in multiple phase II clinical trials for treatment of the breast cancer and renal cell cancer.

Sagopilone (BAY86-5302; ZK 219477; ZK-EPO) is a synthetic epothilone, an analog of patupilone that was developed by Bayer HealthCare as an anticancer agent. Epothilones are 16-member ring macrolides have demonstrated potent antiproliferative activity in several different multidrug-resistant and paclitaxel-resistant tumor cell lines in vitro and in vivo. Sagopilone binds to tubulin and induces microtubule polymerization, which may result in the induction of G2/M arrest, and apoptosis. Sagopilone is not a substrate for the P-glycoprotein efflux pump and so may exhibit activity in multidrug-resistant tumors. This drug was studied in clinical trials phase II in patients with recurrent ovarian cancer, in metastatic melanoma patients, for the treatment of advanced stage breast cancer and in the treatment of Glioblastoma patients. However, the development of this drug was discontinued, because of its adverse effects, including peripheral neuropathy.

Bristol-Myers Squibb developed BMS-275183 for cancer indications. BMS 275183 is an inhibitor of tubulin polymerization. The drug participated in phase II clinical trials for patients with non-small cell lung cancer and in phase I for patients with advanced cancer. However, further development has been discontinued.

Simotaxel (MST-997) is a semi-synthetic, orally bioavailable, third-generation taxane derivative and microtubule-stabilizing agent, with potential antineoplastic activity. Simotaxel was being developed through a collaboration between Wyeth (later Pfizer) and Taxolog as a potential treatment for cancer. Upon administration, simotaxel binds to tubulin, promotes microtubule assembly and stabilization, and prevents microtubule depolymerization. This results in G2/M arrest, apoptosis and the inhibition of cell proliferation in susceptible tumor cells. This agent is a poor substrate for P-glycoprotein-related drug resistance mechanisms; therefore, it may be useful for treating multi-drug resistant tumors. MST-997 is more potent than paclitaxel and docetaxel and overcomes paclitaxel and docetaxel resistance in certain tumor cell types. Simotaxel is under investigation in clinical trial NCT00088647 (study evaluating MST-997 in advanced malignant solid tumors).

Litronesib is a specific, ATP-uncompetitive, allosteric, and potent small-molecule inhibitor of Eg5 with potential antineoplastic activity. Litronesib selectively inhibits the activity of Eg5, which may result in mitotic disruption, apoptosis and consequently cell death in tumor cells that are actively dividing. Histone-H3 phosphorylation of tumor and proliferating skin cells is a promising pharmacodynamic biomarker for in vivo anticancer activity of litronesib. Litronesib had been in phase I clinical trial for the treatment of solid tumors. The most frequent-related adverse events were hematologic such as neutropenia.

Fosbretabulin (Combretastatin A4 phosphate, CA4P) is the lead compound of a relatively new class of agents termed vascular disrupting agents that target existing tumor blood vessels. Rapid tumor blood flow shutdown has been demonstrated in preclinical models and patients by various techniques such as dynamic contrast-enhanced MRI, perfusion computed tomography and PET scans following CA4P infusion. CA4P typically induces rapid tumor necrosis in the center of the tumor and leaves a rim of viable cells in the periphery. In oncology, CA4P does not appear to be that active by itself, but may be more efficacious when combined with chemotherapy, antiangiogenic therapy and radiation therapy. Combretastatin was initially isolated from the root bark of the South African Bush willow Combretum caffrum in 1982 by Pettit and colleagues at the Arizona State University (AZ, USA). Combretastatin A4 phosphate binds avidly to tubulin at the colchicine-binding site to inhibit microtubule assembly and destabilize the cytoskeleton. CA4P is a tubulin-binding agent that binds at or near the colchicine binding site of β-tubulin (Kd = 0.40 uM), inhibits tubulin assembly with IC50 of 2.4 uM. Fosbretabulin has orphan drug status in the EU and the US for the treatment of ATC (Anaplastic Thyroid Cancer). Later the development of this drug was discontinued.