Phosphate Protected Nucleotide Prodrugs

Nucleosides work by mimicking cellular nucleotides (the building blocks of RNA and DNA) and inhibit RNA or DNA synthesis.  A nucleoside is unphosphorylated and must rely on cellular enzymes to attach phosphate groups to create active nucleotide compounds.  Nucleoside drugs often cannot be given in combination since the two drugs in the combination would both need to be phosphorylated inside cells and thus compete for the same enzymes.  Alios scientists, working in collaboration with the world renowned nucleotide chemist Harry Lundberg, Ph.D. at the University of Turku, have synthesized phosphate protected nucleotide prodrugs, and have demonstrated that cellular enzymes can metabolize the protected prodrugs into authentic nucleotide-monophosphate analogs.

The first of these drug candidates is a phosphate protected nucleotide prodrug directed against HCV. Utilizing the Alios proprietary phosphate protected nucleotide prodrug chemistry, the company is advancing clinical candidate compounds that have the potential to be given a substantially lower doses compared to the nucleosides used thus far and may therefore avoid or diminish the related toxicities previously seen.