Preferred Label : RNR Inhibitor COH29;
NCIt synonyms : N-(4-(3,4-dihydroxyphenyl)-5-phenylthiazol-2-yl)-3,4-dihydroxybenzamide; Ribonucleotide Reductase Holoenzyme Inhibitor COH29;
NCIt related terms : COH-29;
NCIt definition : An orally available, aromatically substituted thiazole and inhibitor of the human
ribonucleotide reductase (RNR), with potential antineoplastic activity. Upon oral
administration, the RNR inhibitor COH29 binds to the ligand-binding pocket of the
RNR M2 subunit (hRRM2) near the C-terminal tail. This blocks the interaction between
the hRRM1 and hRRM2 subunits and interferes with the assembly of the active hRRM1/hRRM2
complex of RNR. Inhibition of RNR activity decreases the pool of deoxyribonucleotide
triphosphates available for DNA synthesis. The resulting decrease in DNA synthesis
causes cell cycle arrest and growth inhibition. In addition, this agent may inhibit
the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 1, which prevents the repair
of damaged DNA, and causes both the accumulation of single and double strand DNA breaks
and the induction of apoptosis. 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.;
UNII : 07802BU06S;
InChIKey : LGGDLPSXAGQFSG-UHFFFAOYSA-N;
CAS number : 1190932-38-7;
Molecule name : COH-29;
Origin ID : C114976;
UMLS CUI : C3896727;
Automatic exact mappings (from CISMeF team)
- Semantic type(s)
- chemical_or_drug_affects_gene_product
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
