Gemcitabine-Phosphoramidate Hydrochloride NUC-1031
A pyrimidine analogue and a proprietary prodrug based on an aryloxy phosphoramidate derivative of gemcitabine with potential antineoplastic activity. Upon intravenous administration and cellular uptake, NUC-1031 is converted into the active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA replication; dFdCTP is incorporated into DNA, resulting in premature termination of DNA replication and eventually induction of apoptosis. With the phosphoramidate moiety on the gemcitabine monophosphate group, NUC-1031 has improved properties over its parent molecule: 1) is more lipophilic and accumulates in cancer cells by passive diffusion and does not require a nucleoside transporter, 2) as the agent is delivered in the monophosphate form, the first phosphorylation step by deoxycytidine kinase is not required, 3) this agent is not susceptible to deactivation by cytidine deaminase cleavage of the monophosphorylated form. Altogether, this may help overcome resistance to gemcitabine. [ ]
Term info
Gemcitabine-Phosphoramidate Hydrochloride NUC-1031
- Acelarin
- Gemcitabine-Phosphoramidate Hydrochloride NUC-1031
- Gemictabine ProTide
- NUC-1031
NCIT_C116978, NCIT_C128784, NCIT_C116977, NCIT_C157711, NCIT_C157712
CTRP
Gemcitabine-Phosphoramidate Hydrochloride NUC-1031
735822
735822
Gemcitabine-Phosphoramidate Hydrochloride NUC-1031
Pharmacologic Substance, Nucleic Acid, Nucleoside, or Nucleotide
C3640933
C102752
Term relations
- Ribonucleotide Reductase Inhibitor
- Pyrimidine Antagonist
- Chemical_Or_Drug_Has_Physiologic_Effect some DNA Synthesis Inhibition
- Chemical_Or_Drug_Has_Mechanism_Of_Action some Enzyme Inhibition
- Chemical_Or_Drug_Has_Physiologic_Effect some Positive Regulation of Apoptosis
- Chemical_Or_Drug_Affects_Gene_Product some Ribonucleotide Reductase
- Chemical_Or_Drug_Has_Physiologic_Effect some Nucleotide Biosynthesis Process