Dolastatin 10 is an unusual peptide of marine origin which binds to tubulin, inhibits microtubule assembly, resulting in the formation of tubulin aggregates and inhibition of mitosis. Dolastatin 10 has been used in trials phase II studying the treatment of Sarcoma, Leukemia, Lymphoma, Liver Cancer, among others. In case of hormone-refractory prostate cancer, it lacks significant clinical activity as a single agent and also dolastatin-10 is inactive against hepatobiliary and pancreatic carcinomas.

MKC-1 is an orally available cell cycle inhibitor with downstream targets that include tubulin and the importin-β family. MKC-1 has shown broad antitumor activity in preclinical models. MKC-1 and its metabolites inhibit tubulin polymerization, blocking the formation of the mitotic spindle, which may result in cell cycle arrest at the G2/M phase and apoptosis. In addition, this agent has been shown to inhibit the activities of the oncogenic kinase Akt, the mTOR pathway, and importin-beta, a protein essential to the transport of other proteins from the cytosol into the nucleus. MKC-1 had been in phase II clinical trials for the treatment of ovarian cancer, endometrial cancer, pancreatic cancer and breast cancer. This compound was originally discovered by Roche, then licensed to EntreMed (now CASI Pharmaceuticals) the exclusive worldwide rights to develop and commercialize. However, no recent development has been reported.

Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

Taltobulin, also known as HTI-286 and SPA-110, is a fully synthetic analog of the natural tripeptide hemiasterlin, inhibits tubulin polymerization and circumvents transport-based resistance to taxanes. Taltobulin was a potent inhibitor of proliferation (mean IC50 = 4 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine. Taltobulin showed strong antitumor activity both in androgen-dependent and androgen- independent tumors and may be a promising agent in second- line treatment strategies for patients suffering from docetaxel- refractory prostate cancer.

2-Methoxyestradiol (2ME2) is a natural metabolite of endogenous estrogen hormone 17β-estradiol in human and devoid of estrogenic activity. It is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It has undergone Phase 1 clinical trials against breast cancers. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. 2-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. 2-Methoxyestradiol shows strong cytotoxic effect on estrogen dependent and independent cancerous cells, which is mainly due to disruption of microtubule process and p53 induced apoptosis through caspase, reactive oxygen species (ROS), superoxide dismutase (SOD) and nitric oxide synthase. 2-Methoxyestradiol inhibits tubulin polymerisation by binding to colchicine binding site of the tubulin and arrests cell cycle at G2/M-phase.

Monomethyl Auristatin E (MMAE) is an antimitotic agent which inhibits cell division by blocking the polymerization of tubulin. Monomethyl Auristatin E is the synthetic analog of the antineoplastic natural product Dolastatin 10, cannot be used as a drug itself. Monomethyl Auristatin E is commonly conjugated with monoclonal antibodies directed at antigens specific to cancer cells for tumor-directed cytotoxicity. MMAE is typically coupled to the antibody via a protease-cleavable linker, allowing separation of the drug from the antibody following intracellular localization. When coupled to cAC10, Monomethyl Auristatin E shows selective cytotoxicity in CD30+ cells and induces G2/M-phase growth arrest and cell death through the induction of apoptosis. When coupled to the anti-CD79b antibody, anti–CD79b-vcMMAE has very potent and broad activity across a large panel of NHL cell lines in vitro. When coupled to the anti-HER2 antibody, pertuzumab-vc-MMAE can also be effectively internalized and potently kill HER2 over-expressing tumor cells. In the Karpas 299 ALCL model, cAC10-vcMMAE induces complete, durable tumor regression, while free MMAE doesn’t produce detectable antitumor activity. In mouse xenograft models of NHL, anti–CD79b-vcMMAE strikingly results in sustained complete tumor remission.

Tubulysin A is a myxobacterial product that can function as an antiangiogenic agent in many in vitro assays. Tubulysin A is a novel antibiotic, which is anti-microtubule, anti-mitotic, apoptosis inducer, anticancer, anti-angiogenic, and antiproliferative. Tubulysins are cytotoxic peptides, which include 9 members (A-I). Tubulysin A has potential application as an anticancer agent. It arrests cells in the G2/M phase. Tubulysin A inhibits polymerization more efficiently than vinblastine and induces depolymerization of isolated microtubules. Tubulysin A has potent cytostatic effects on various tumor cell lines with IC50 in the picomolar range.