NCIt 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.;