Highlights
- DZ-2384 is a refined synthetic derivative of the natural product, Diazonamide A.
- It targets the mitotic pathway by a novel mechanism of action, and is potentially lethal to cancer cells with improved safety margins compared to the other microtubule targeting agents.
- Potent single agent anti-tumor activity across multiple xenograft models
- Safety margins and mechanism suggest opportunities for rational combination therapies
- Currently in pre-clinical development
Description
Diazon Pharmaceuticals was formed in October 2013 to develop DZ-2384, a novel anti-cancer agent that interferes with cell division in a previously undescribed manner. This compound exhibits highly potent anti-cancer activity in both tissue culture and xenograft tumor models in mice, with unusually favorable safety margins. Therillia, in partnership with the Laboratory for Therapeutic Development at the Rosalind and Morris Goodman Cancer Research Center of McGill University, has recently determined the mechanism of action (MoA) of DZ-2384 as a tubulin inhibitor, exhibiting a novel binding mode at the vinca site with distinct results. In contrast to the taxanes, which stabilize microtubules, and the vincas, which depolymerize microtubules, DZ-2384 largely preserves the microtubule network in interphase cells, including in neurons. In pre-clinical rodent models, no neuropathy was observed at DZ-2384 levels that are efficacious. The potent efficacy and favorable safety margins of DZ-2384 suggest several strategies for confirming clinical proof of concept in indications where taxanes or vinca alkaloids are the current standard of care. Moreover, and in contrast to other anti-mitotics, the potential for combination therapies as a result of DZ-2384 safety, including in immuno-oncology, is highly attractive.
DZ-2384 is currently in advanced preclinical development.