Vanadium Compounds as Insulin-enhancing Pharmaceuticals
Vanadium has been known to have insulin-mimetic properties in vitro for decades; it was our collaborator, Prof. John McNeill of UBC’s Faculty of Pharmaceutical Sciences, who showed in an animal model (the STZ-diabetic rat) in 1985 that these properties could be used as a treatment in vivo. Naturally, to progress the field required designed pertinent compounds of vanadium, particularly for structure-activity relationships and for increased oral absorption, the key property necessary for agents with clinical potential in diabetes treatment. Many vanadium compounds are now reported to have insulin-enhancing properties, most notably when administered orally (a route via which insulin is not active). Still, gastrointestinal absorption of vanadium is usually poor and depends on the chemical nature, solubility, and speciation of the specific metal ion complex. Little is known about the coordination properties of orally administered vanadium compounds in vivo, about the factors required to deliver vanadium to its ultimate site of action, or indeed the site of action.
Over a period of 20 years, we designed, synthesized and studied in detail vanadium compounds of the widely-used food additives maltol and ethylmaltol, bis(maltolato)oxovanadium(IV) (BMOV) and bis(ethylmaltolato)oxovanadium(IV) (BEOV), as well as of many other ligands. After preliminary studies of oral efficacy in diabetic rats, the use of this compound for a variety of indications was patented by UBC and the initial results were published in 1992 to significant notice. Subsequently, the research was licensed and many collaborative studies of the coordination chemistry and biological efficacy were undertaken in the labs of Orvig and McNeill. Because of its oral efficacy and lack of toxicity, BMOV has become the benchmark for oral vanadium-containing insulin-enhancing compounds. In 2008, BEOV completed a small phase IIa clinical trial for diabetes mellitus but UBC's patent protection expired in September 2011 and, while we do not work in this area any longer, we hope to see this system become a generic drug in the future.