Preferred Label : 3'-dA Phosphoramidate NUC-7738;
NCIt synonyms : Nucleoside Analog NUC-7738;
NCIt definition : A phosphoramidate derivative of the monophosphate form of cordycepin (3'-deoxyadenosine;
3'-dA), an adenosine derivative first isolated from Cordyceps sinensis, with potential
antineoplastic, antioxidant, and anti-inflammatory activities. Upon administration
and cellular uptake of NUC-7738 by passive diffusion, cordycepin monophosphate (3'-dAMP)
is converted into its active anti-cancer metabolite 3'-deoxyadenosine triphosphate
(3'-dATP). 3'-dATP functions as a ribonucleoside analogue and competes with ATP during
transcription. Therefore, this agent causes RNA synthesis inhibition, inhibits cellular
proliferation, and induces apoptosis. Also, 3'-dAMP activates AMP-activated protein
kinase (AMPK) and reduces mammalian target of rapamycin (mTOR) signaling. This prevents
the hyperphosphorylation of the translation repressor protein 4E-BP1. This results
in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation.
mTOR, a serine/threonine kinase belonging to the phosphatidylinositol 3-kinase (PI3K)-related
kinase (PIKK) family, plays an important role in the PI3K/AKT/mTOR signaling pathway
that regulates cell growth and proliferation, and its expression or activity is frequently
dysregulated in human cancers. Compared to cordycepin alone, the addition of the phosphoramidate
moiety may overcome cancer resistance and allow for greater cytotoxicity as NUC-7738
does not require a nucleoside transporter for cellular uptake, is independent of enzymatic
activation by adenosine kinase (AK) and is not susceptible to enzymatic degradation
by adenosine deaminase (ADA). Altogether, this may help overcome cancer resistance
to cordycepin.;
Molecule name : NUC-7738; NUC 7738;
NCI Metathesaurus CUI : CL1405486;
Origin ID : C171381;
UMLS CUI : C5417858;
Semantic type(s)
- concept_is_in_subset
