The study, titled “The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity,” by Michal Wieczorek et al., highlights distinct structural features of DZ-2384 binding to tubulin that help preserve the cell microtubular infrastructure of neurons and non-dividing cells, resulting in lower toxicity. DZ-2384’s novel mechanism of action was shown to result in unique effects on microtubule curvature and dynamics distinct from other agents in its class.
Anti-mitotic tubulin-binding agents constitute part of the standard-of-care in over 15 different oncology indications. Treatment is accompanied by significant toxicities including neurotoxicity that often limit their use and effectiveness. In contrast, DZ-2384 did not cause peripheral neuropathy at efficacious doses, yet retained potent activity in preclinical models.
Diazon partnered with the Laboratory for Therapeutic Development at the Rosalind and Morris Goodman Cancer Research Center, McGill University to elucidate DZ-2384’s mechanism of action and to determine which cancers are likely to derive the most therapeutic benefit from this agent. The research was led by Drs. Anne Roulston and Gordon Shore of the Laboratory for Therapeutic Development and Dr. Gary Brouhard at the University’s Department of Biology and included several international collaborators.
Anne Roulston, Ph.D., associate director of the Laboratory for Therapeutic Development at the Goodman Cancer Research Center, McGill University, said “The data provide us with key insights into the basic attributes of DZ-2384 and demonstrate preclinical proof of its validity as a new generation of chemotherapy. Such a drug could be used both as sole treatment or in combination with other therapies, such as immuno-oncology. We believe DZ-2384 has the potential to be a highly effective and safer alternative to current anti-mitotic agents.”
November 24, 2016