5'-Nucleotidase Overview
5'-Nucleotidase is an enzyme that catalyzes the hydrolysis of phosphate groups from nucleoside monophosphates at the 5' position, producing corresponding nucleosides and inorganic phosphate[2][4]. It exists both as a soluble cytoplasmic enzyme involved in nucleotide metabolism and as a membrane-bound ectoenzyme—most notably known as CD73—which plays a key role in generating extracellular adenosine from AMP[2][6]. This activity regulates purinergic signaling with broad implications for immune modulation, vascular function, inflammation control, and cancer biology[1][2][6]. The enzyme has wide substrate specificity but primarily acts on AMP; its activity can influence resistance mechanisms against certain chemotherapeutic agents by dephosphoryting active drug metabolites[5].
Mechanism of Action
Drugs targeting this enzyme typically act as inhibitors to block the conversion of AMP to adenosine, thereby reducing immunosuppressive signaling mediated by adenosine in the tumor microenvironment or inflamed tissues.
Biological Functions
Disease Associations
Safety Considerations
- Potential safety concerns include impaired tissue protection during hypoxia or ischemia due to reduced adenosine production
- increased risk of inflammation or autoimmunity from loss of immunoregulatory effects
- possible off-target effects due to broad tissue distribution[2][6]
Associated Biomarkers
Biomarker |
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CD73 expression is used as a biomarker for certain cancers and may be used for patient selection in clinical trials involving anti-CD73 therapies. |