Precise Targeting of Nucleotide Metabolism for the Treatment of Cancers and Autoimmune Diseases
Deoxycytidine Kinase (dCK) has been implicated in abnormal cell proliferation. Our dCK inhibitor, TRE-515, has been chemically engineered to improve bioavailability and demonstrates robust target binding.
A first-in-class inhibitor for autoimmune diseases and cancers
TRE-515 is a potent and orally-bioavailable inhibitor of dCK that may have monotherapy activity against solid tumors where low expression of the de novo pathway or other metabolic changes occur creating greater sensitivity to nucleotide salvage pathway inhibition.
Overactivation of T cells, B cells, or both has been observed in certain autoimmune diseases. Inhibition of dCK, by TRE-515, can create favorable immunomodulatory properties in a monotherapy context for some autoimmune syndromes.
A novel attack on salvage pathway requiring diseases
Human cell nucleotide synthesis occurs via either the salvage pathway (regulated by deoxycytidine kinase, dCK) or the de novo pathway (regulated by dihydroorotate dehydrogenase, DHODH and ribonucleotide reductase, RNR). Unfortunately, treatments today focus on blocking the de novo pathway, leading to drug resistance. Trethera is developing a platform of drugs attacking different points in cell nucleotide metabolism.