Thymidylate synthase destabilizer E7 is a small molecule human thymidylate synthase (hTS) destabilizer, binds at the monomer-monomer interface and shifts the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers.
Thymidylate synthase destabilizer E7 is a small molecule human thymidylate synthase (hTS) destabilizer, binds at the monomer-monomer interface and shifts the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers.
E7 induced apoptosis in cancer cells and a decrease of hTS levels due to enhanced proteasomal degradation of the enzyme monomers with respect to the dimers.
E7 caused a higher reduction of cancer growth and had lower toxicity than 5-fluorouracil (5-FU), the prodrug of 5-FdUMP, in a mouse model of orthotopic pancreatic cancer.
