Preferred Label : Fosdesdenosine Sipalabenamide;
NCIt synonyms : Nucleoside Analog NUC-7738; 3'-dA Phosphoramidate 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 fosdesdenosine sipalabenamide 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 fosdesdenosine sipalabenamide 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.;
UNII : Y7BFN2M72F;
CAS number : 2348493-39-8;
Molecule name : NUC-7738; NUC 7738;
NCI Metathesaurus CUI : CL1405486;
Origin ID : C171381;
UMLS CUI : C5417858;
Semantic type(s)
- UMLS correspondences (same concept)
- concept_is_in_subset
