Gatorbulin-1, a Microtubule-Destabilizing Agent for Disrupting Cancerous Tumors

Targets a Newly Identified Tubulin Binding Site to Destabilize Tubulin

This microtubule-destabilizing agent, derived from a marine cyanobacterium, targets a new seventh tubulin-binding site and inhibits cancer cell growth. Tubulin-targeting chemotherapy is a proven successful and wide-spectrum strategy against multiple solid and liquid malignancies. In 2019, the United States reported over 1.7 million new cancer cases, leading to approximately 600,000 deaths. In 2021, the chemotherapy drug market had a value of $42.9 million and could reach $89 million by 2029. Previously, known tubulin-targeting agents bind to six sites at the α/β-tubulin heterodimer, leading to microtubule depolymerization or stabilization. Available microtubule-destabilizing compounds are frequently toxic. Since anticancer efficacy and the pharmacological effects vary depending on the chemical scaffold and binding sites, there is a continued demand for new microtubule-targeting agents against novel binding sites.

Researchers at the University of Florida have discovered gatorbulin-1 (GB1), a new microtubule-destabilizing cyclodepsipeptide that binds to a new seventh binding site near the colchicine site. Derived from a marine cyanobacterium, GB1 may lead to a treatment method for patients suffering from or susceptible to proliferation diseases or disorders, such as cancer, providing treatments with lower toxicity.

Application

Gatorbulin-1 (GB1), a microtubule-destabilizing agent, targets and binds to a new seventh tubulin-binding site, inhibiting cancer cell proliferation

Advantages

• GB1 binds to a novel tubulin site, leading to the development of new anticancer treatments with lower toxicity
• GB1 does not significantly affect non-cancer cell lines in vitro, potentially translating into low toxicity in vivo
• Low molecular weight compared with other tubulin inhibitors and scalable chemical synthesis, adding to its promising drug-like properties and translational potential
• Multiple cancer cell lines, including colon, melanoma, ovarian, and prostate cancer lines, show susceptibility to GB1, making it a potential chemotherapeutic agent against different malignancies

Technology

Gatorbulin-1 (GB1), a microtubule-destabilizing cyclodepsipeptide derived from a marine cyanobacterium, presents a distinct chemotype and binds to a seventh microtubule pocket situated between α- and β-tubulin, near the colchicine site. Through binding to this new site, GB1 destabilizes microtubule formation through a wedging mechanism. Tubulin is a crucial target for the development of chemotherapeutics, so targeting it yields increased drug screening possibilities and the development of safer and more effective cancer treatment options, alone or as an antibody-drug conjugate (ADC).