Target intelligence / Profile preview

5′-nucleotidase (ecto-5′-nucleotidase; CD73) (CD73)

Target
CD73
Molecular classification
Enzyme, Ectoenzyme, GPI-anchored membrane protein
01

Overview

5′-nucleotidase (CD73) is a glycosylphosphatidylinositol-anchored dimeric ectoenzyme, encoded by the NT5E gene, located on the external face of cell membranes, notably lymphocytes and endothelial cells. Its primary function is the hydrolysis of extracellular AMP to adenosine, which orchestrates a wide range of purinergic signaling pathways, particularly those controlling inflammation, vascular permeability, immune cell activation, and barrier function. CD73 is a critical regulator of immune homeostasis, limiting pro-inflammatory signals and generating anti-inflammatory adenosine, thus contributing both to protection in chronic inflammatory conditions and to immunosuppression in cancers and certain pathologies. Both membrane-bound and soluble forms exist, with the latter found in extracellular vesicles and body fluids, especially at sites of inflammation and cancer. CD73's catalytic pocket and conformational dynamics provide key pharmacological access points for therapeutic intervention, where inhibition can disrupt tumor-induced immune suppression but may also risk tissue dysfunction in organs dependent on CD73-mediated adenosine signaling.

Other names
Ecto-5′-nucleotidaseNT5E (gene symbol)5′-nucleotidase (sometimes written as 5'-nucleotidase)Cluster of differentiation 73
02

Mechanism of action

Inhibition of enzymatic activity, reducing adenosine production to promote anti-tumor immunity Antibody-mediated block of enzyme conformational change (prevents closed active state) Small-molecule inhibition of the catalytic pocket (competitive inhibition)

03

Biological functions

Catalyzes the conversion of extracellular AMP to adenosineRegulates immune response (converts proinflammatory ATP/ADP to anti-inflammatory adenosine)Modulates inflammation and immune suppressionRegulates vascular and tissue barrier function (e.g., respiratory system permeability, renal function)Marker of lymphocyte differentiation
04

Disease associations

Cancer (promotes immunosuppressive tumor microenvironment)Inflammation (regulates pro- and anti-inflammatory balance)Cardiovascular disease (protection in heart failure models)Immunodeficiency (deficiency can lead to immunodeficiency diseases)Kidney injury (role in renal protection and injury modulation)
05

Safety considerations

Systemic inhibition may impair tissue protection (especially cardiac and renal protection)Impact on immune regulation and potential for promoting unwanted inflammation or tissue disruption
06

Interacting drugs

Various experimental small-molecule inhibitors of CD73 (notably targeting the catalytic pocket)

2 more in the full profile.

07

Biomarkers

CD73 levels as a marker of immunosuppressive tumor environmentsUsed as a marker in lymphocyte differentiationSoluble CD73 detected as a biomarker in inflammation and cancer

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