Triapine^®

 

Triapine^®, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), is a small molecule chelator that inhibits the enzyme ribonucleotide reductase and therefore prevents the replication of tumor cells by blocking a critical step in DNA synthesis. Inhibition of this enzyme has been shown in vitro and in vivo to enhance the anti-tumor activity of several standard anticancer agents and enhance tumor sensitivity to radiation treatment. DNA synthesis disruption is due in part to the effective ability of Triapine® to chelate iron intracellularly. Some tumors have been shown to be sensitive to iron chelator therapy which provides a useful target for anti-cancer drugs and results in tumor cell death.

 

Triapine^® is being developed by Nanotherapeutics for the treatment of solid tumors such as cervical and vaginal cancers. Nanotherapeutics acquired the Triapine® program in 2011 and is continuing an already extensive clinical program. This small molecule was discovered in the laboratory of Alan Sartorelli, Ph.D. at Yale University. Triapine® has been tested in clinical trials in an intravenous formulation and an oral formulation. Both formulations are currently being developed.

 

Triapine^® has been evaluated in over twenty Phase 1 and Phase 2 clinical trials. The National Cancer Institute has been actively involved with clinical trials involving Triapine^®. The NCI's Cancer Therapy Evaluation Program has sponsored 19 Phase 1 and Phase 2 trials using Triapine^®. One of the on-going clinical trials assesses the safety and clinical activity of 3x weekly intravenous administrations of Triapine^® co-administered with 1x weekly intravenous cisplatin and daily pelvic radiation in patients with locally advanced cervical and vaginal cancer. This regime was shown to be well tolerated and associated with a high clinical and metabolic response. Further accrual is on-going. The positive interim results were presented at the 2011 ASCO Annual Meeting. Larger studies are being planned to confirm the exciting Phase 1/2 results and hopefully bring Triapine® to patients in need of improved cancer treatments.