Definition

An orally available human ribonucleotide reductase (RNR) subunits interaction inhibitor, with potential antineoplastic and immunomodulating activities. Upon oral administration, the RNR subunits interaction inhibitor TAS1553 blocks the protein-protein interaction between and interferes with the assembly of the RNR subunits R1 and R2. This prevents RNR activity and decreases the pool of deoxyribonucleotide triphosphates (dNTPs) available for DNA synthesis. The resulting decrease in DNA synthesis causes cell cycle arrest and growth inhibition. In addition, this agent may have immunomodulatory effects on the tumor microenvironment (TME), may increase the number of CD8+ T-cells and may increase the expression of interferon gamma (IFNg) in tumors. RNR, an enzyme that catalyzes the conversion of ribonucleoside diphosphate to deoxyribonucleoside diphosphate, is essential for de novo DNA synthesis and plays an important role in cell growth; it is overexpressed in many cancer cell types and is associated with increased drug resistance, cancer cell growth and metastasis.