Crolibulin is a tubulin-disrupting agent, interacting at the colchicine-binding site, developed by EpiCept Corporation (which was later acquired by Immune Pharmaceuticals). The compound exhibits anti-cancer effect by vascular disruption and inhibition of apoptosis. In preclinical animal tumor models, combination therapy with crolibulin has demonstrated the synergistic activity with cytotoxic drugs as well as anti-angiogenic drugs, such as Avastin. The drug was investigated in clinical trials for the treatment of anaplastic thyroid cancer and has demonstrated a positive effect.

Plinabulin (formerly known as NPI-2358) is a potent microtubule-destabilizing agent that exerts its effect by binding to the colchicine-binding site of tubulin. Plinabulin projects its potent antitumor activity against a broad spectrum of tumor cell lines. This drug in combination with docetaxel is under development by BeyondSpring Pharmaceuticals in a worldwide Phase 3 clinical trial for non-small cell lung cancer. Pegfilgrastim is also in phase II clinical trial for the prevention of chemotherapy-induced neutropenia, where docetaxel, doxorubicin, and cyclophosphamide (TAC) were used as the chemotherapy. Plinabulin also possessed antitumor activity in animal models with multiple myeloma cancer cells, where the JNK protein appeared to be a primary target of plinabulin.

Tasidotin (also known as ILX-651), an orally active synthetic microtubule-targeted derivative of the marine depsipeptide dolastatin-15. It was suggested, that tasidotin has a unique mechanism of action. The drug inhibits cell proliferation by suppressing spindle microtubule dynamics through a reduction of the shortening rate, reduction of the switching frequency from growth to shortening, and reduction of the time microtubules grow. Tasidotin was studied in clinical trials phase II in patients with locally advanced or metastatic non-small cell lung carcinoma, in patients with hormone-refractory prostate cancer, and in patients with inoperable locally advanced or metastatic melanoma. However, no new results were published last 5 years. It was suggested that tasidotin is no longer being used as single or even components of multiple agents today.

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.

Mivobulin is a synthetic water-soluble colchicine analog with the broad antitumor activity that competitively binds tubulin at the colchicine-binding site and inhibits tubulin polymerization. Cancer cells exposed to Mivobulin isethionate accumulate in the M phase of the cell cycle and subsequently die. Preclinical studies have demonstrated that Mivobulin isethionate is able to cross the blood-brain barrier. Importantly, Mivobulin isethionate demonstrated significant antitumor activity in a broad spectrum of murine and human tumor models that were cross-resistant to vincristine, cisplatin, vinblastine, navelbine, and doxorubicin and in tumor cell lines exhibiting multidrug resistance owing to P-glycoprotein overexpression. In animal studies, the activity of Mivobulin isethionate was largely independent of the route of drug administration but favored a prolonged treatment schedule. Unfortunately, in clinical trials, Mivobulin fail to demonstrate the significant activity

CYT997 (Lexibulin) is a wholly synthetic compound that possesses highly potent cytotoxic activity in vitro through inhibition of microtubule polymerization. CYT997 (Lexibulin) is a potent microtubule polymerization inhibitor with IC50 of 10-100 nM in cancer cell lines. CYT997 (Lexibulin) blocks the cell cycle at the G(2)-M boundary, and Western blot analysis indicates an increase in phosphorylated Bcl-2, along with increased expression of cyclin B1. Caspase-3 activation is also observed in cells treated with CYT997 (Lexibulin) along with the generation of poly(ADP-ribose) polymerase. The compound possesses favorable pharmacokinetic properties, is orally bioavailable, and is efficacious per os in a range of in vivo cancer models, including some refractory to paclitaxel treatment. CYT997 (Lexibulin) exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 (Lexibulin) possesses a useful combination of pharmacologic and pharmacokinetic properties having considerable potential as a novel anticancer agent. Lexibulin was being developed by YM BioSciences as a vascular-disrupting agent (VDA) for the potential treatment of cancer, it was in phase II development on YM BioSciences ' pipeline. It appears that the development of lexibulin has been discontinued.

Denibulin is a novel antineoplastic agent. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation. Denibulin hydrochloride had been in phase I clinical trials for the treatment of solid tumours. It was generally well tolerated and showed decrease in tumor vascular parameters. However, no recent development has been reported.

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.

Batabulin or T138067 (2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene) covalently and selectively modifies the beta1, beta2, and beta4 isotypes of beta-tubulin at a conserved cysteine residue, thereby disrupting microtubule polymerization. Cells exposed to batabulin become altered in shape, indicating a collapse of the cytoskeleton, and show an increase in chromosomal ploidy. Batabulin is equally efficacious in inhibiting the growth of sensitive and multidrug-resistant human tumor xenografts in athymic nude mice. Batabulin has been in clinical trials for the treatment of cancers (breast cancer, colorectal cancer, glioma, hepatocellular carcinoma, non-small cell lung cancer). It does not have clinical activity in the treatment of colorectal cancer and glioma. Batabulin 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).