A compound derived from the thunder god vine used widely in Chinese medicine has shown dramatic results in the treatment of pancreatic cancer in multiple mouse models, and is projected to start in clinical trials by the end of the year. The new drug, called minnelide, is a modified form of the diterpenoid compound triptolide, isolated from the medicinal vine Tripterygium wilfordii. Previous studies have found triptolide has potent activity against a range of tumor types, but the drug is only poorly soluble in water, which has made its potential use as a chemotherapeutic agent problematic.
A multidisciplinary team of researchers at the University of Minnesota has now synthesized a highly water-soluble analog of triptolide, which is effectively converted back to the parent drug in the presences of phosphatases, which are naturally found in all body tissues, including the blood. The investigators’ studies in pancreatic cell lines showed that minnelide significantly reduced cancer cell viability. More encouragingly, in vivo experiments in a number of different orthotopic, human xenograft, and spontaneous mouse models of pancreatic cancer showed minnelide to be highly effective at reducing tumor burden and locoregional spread, and increasing survival, even in animals carrying orthotopic tumors derived from highly metastatic cancer cell lines. Tests in one orthotopic model of pancreatic cancer showed minnelide was even more effective than gemcitabine at reducing tumor volume.
Rohit Chugh, M.D., Ashok K. Saluja, M.D., and colleagues report on the synthesis of minnelide and their in vitro and in vivo studies in Science Translational Medicine. “Our studies suggest that minnelide is more effective when compared to other potential therapeutics against pancreatic cancer, which have been tested in mouse models,” the authors write. “Our data suggest that minnelide has the potential to emerge as an effective therapy against not only pancreatic cancer but also many other cancers. In this regard, the Phase I trial of minnelide against pancreatic cancer is currently being planned and is scheduled to start by December 2012 (pending FDA approval).”
The team’s paper is titled “A Preclinical Evaluation of Minnelide as a Therapeutic Agent Against Pancreatic Cancer.”