Cemadotin (LU103793) is a cytotoxic water-soluble pentapeptide analogue of dolastatin 15. The dolastatin peptides were originally isolated from the shell-less mollusc Dolabella auricularia. Cemadotin blocks cells at mitosis. It exerts its antitumor activity by suppressing spindle microtubule dynamics through a distinct molecular mechanism by binding at a novel site in tubulin. Cemadotin was in phase II clinical trials as a promising cancer chemotherapeutic agent. However, this agent appears to be inactive in the treatment of advanced non-small-cell lung cancer and other tumors and this research has been discontinued.

LAROTAXEL is a taxoid with potential antineoplastic activity. It prevents microtubule depolymerization, thereby inhibiting cell proliferation. It displays a broad spectrum of antitumor activity in vitro and in vivo, including activity against P-glycoprotein expressing tumors. LAROTAXEL was in phase III clinical trials for the treatment of breast cancer, pancreatic cancer, and bladder cancer. However, its development was discontinued.

Nocodazole is an anti-mitotic drug that has long been used as an experimental tool in cell biology. Nocodazole is known to bind with high affinity to tubulin and to inhibit microtubule assembly. The tubulin molecule is a α/β heterodimer; both α and β exist as various isotypes whose distribution and drug-binding properties are significantly different. Nocodazole has the highest affinity for αβIV and the lowest affinity for αβIII. In addition, nocodazole was investigated as an anticancer drug on xenografts model and it was revealed, that nocodazole possessed a high-affinity for the cancer-related kinases ABL, c-KIT, BRAF, and MEK, and inhibited Abl, Abl(E255K) and Abl(T315I).

ABT-751 is an orally bioavailable antimitotic sulfonamide, which binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 had been in phase Ⅱ clinical studies for the treatment of breast cancer; colorectal cancer; non-small cell lung cancer; renal cancer, prostate cancer, but these researches have been discontinued.

Patupilone is a compound isolated from the myxobacterium Sorangium cellulosum. Similar to paclitaxel, Patupilone induces microtubule polymerization and stabilizes microtubules against depolymerization conditions. In addition to promoting tubulin polymerization and stabilization of microtubules, this agent is cytotoxic for cells overexpressing P-glycoprotein, a characteristic that distinguishes it from the taxanes. Epothilone B may cause complete cell-cycle arrest. Patupilone failed a phase III trial for ovarian cancer in 2010.

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.

Vinrosidine (leurosidine) is a leurosine-like alkaloid originally isolated from Vinca rosea Linn. Vinrosidine exerts antitumor activity in animal models.

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.

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.