Vedotin fragment (Monomethyl auristatin E, MMAE; SGD-1010) is a synthetic derivative of dolastatin 10 and functions as a potent mitotic inhibitor by inhibiting tubulin polymerization. MMAE is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) to treat several different cancer types. MMAE is a potent radiosensitizer. MMAE radiosensitization can be localized to tumors by targeted activatable cell-penetrating peptides.

Lisavanbulin, also known as BAL-101553, a prodrug of the molecule BAL-27862 with potential antitumor activity. BAL-27862 binds to tubulin, prevents tubulin polymerization, destabilizes microtubules, arrests tumor cell proliferation, and induces cell death in cancer cells. Lisavanbulin participated in phase II clinical trials for the treatment of advanced solid tumors. Besides, the drug participates in a 1/2a clinical study in patients with recurrent glioblastoma and in patients with platinum-resistant or refractory ovarian cancer. In this study, will be characterized the safety and tolerability and to obtain efficacy data in these selected cancer types.

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.

KOSN-1724, also known as iso-fludelone, is the third-generation epothilone B analogue. It binds to tubulin and induces microtubule polymerization/reduces microtubule depolymerization, resulting in the inhibition of cell division and induction of apoptosis. KOSN-1724 is in phase I clinical trials for the treatment of solid tumors.

T-900607 is a pentafluorophenylsulphonamide derivative patented by Tularik Inc. as antiproliferative agent. Antitumor mechanism of T900607 is similar to the vinca alkaloids in terms of disruption of microtubule polymerization but uniquely causes a specific covalent modification of β-tubulin. In preclinical studies, T900607 was shown to bind irreversibly and specifically to the β1, β2, and β4 isotypes of β-tubulin is not a substrate for p-glycoprotein drug pump and has activity in the preclinical setting in MDR models. T900607 was evaluated in human tumor xenografts and showed activity in MX-1, MCF-7, and MCF-7/ADR mammary, C13 ovarian, HT 29 colon, and Caki-1 renal carcinoma as well as lymphoblastic leukemia, with equal or more efficacious effects compared to vinblastine, doxorubicin and paclitaxel. In a clinical trial, T-900607 shows significant toxicity, consisting of thrombocytopenia, nausea/vomiting, fatigue, and apparent cardiac toxicity.

Oxi0-4503 (now known as combretastatin A1 phosphate), a diphosphate prodrug of combretastatin A1, was developed by Mateon therapeutics as a second-generation, dual-mechanism vascular disrupting agent from the combretastatin family. On November 21, 2012, Oxi-4503 has been granted orphan designation by the US Food and Drug Administration for the treatment of acute myelogenous leukemia. It is known that the orphan drug designation qualifies a company for several benefits, including the potential for market exclusivity, development grants, and tax credits. Oxi0-4503 is currently participating in phase I/II clinical trial the treatment of patients with acute myelogenous leukemia or myelodysplastic syndrome. In addition, phase I clinical trial was successfully completed where was studied the safety of Oxi0-4503 in patients with advanced solid tumors.

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.

Veribulin is a novel microtubule destabilizer that both functions as a potent cytotoxin and acts as a vascular disrupting agent (VDA). It binds to the same (or nearby) sites on β-tubulin as colchicine. It is capable of evading multidrug resistance pumps and, thus, achieves high CNS concentrations. It is efficacious in multiple xenograft models without CNS toxicity. Veribulin had previously demonstrated pre-clinical and clinical activity in multiple tumor types. Veribulin is in phase II clinical trial for the treatment of Glioblastoma and Malignant melanoma.

Combretastatin is a phenol derivative isolated from the bark of Combretum caffrum, commonly known as South African Bush Willow. Combretastatin is an effective antimitotic agent, and like colchicine, inhibited tubulin polymerization and stimulated tubulin-dependent GTP hydrolysis.

Vinfosiltine (also known as S 12363) was developed as a vinca alkaloid derivative. It is known that vinca alkaloids are widely used in the medical treatment of breast cancer. Vinfosiltine participated in the phase II clinical trial to treat the patients with advanced breast cancer. The results have shown that the drug didn’t have significant single-agent activity. As a result, the development of vinfosiltine was discontinued.