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- Ba216c8779e24249b5a46b597098e1e22 NCIT_P378 "NCI" @default.
- Ba216c8779e24249b5a46b597098e1e22 type Axiom @default.
- Ba216c8779e24249b5a46b597098e1e22 annotatedProperty IAO_0000115 @default.
- Ba216c8779e24249b5a46b597098e1e22 annotatedSource NCIT_C102752 @default.
- Ba216c8779e24249b5a46b597098e1e22 annotatedTarget "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, fosgemcitabine palabenamide 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." @default.