The CD73 is induced by TGF-β1 triggered by nutrient deprivation and highly expressed in dedifferentiated human melanoma.

CD73 is the key enzyme in the generation of extracellular adenosine, a mediator involved in tumor progression, tumor immune escape and resistance to anti-cancer therapeutics. Microenvironmental conditions influence the expression of CD73 in tumor cells. However how CD73 expression and activity is regulated in a stress condition of lower nutrient availability are largely unknown.

CD73 controls ocular adenosine levels and protects retina from light-induced phototoxicity.

ATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning and neurovascular coupling in the mammalian eye. However, little is known about the regulatory mechanisms of purinergic signaling in the eye. Here, we used three-dimensional multiplexed imaging, in situ enzyme histochemistry, flow cytometric analysis, and single cell transcriptomics to characterize the whole pattern of purine metabolism in mouse and human eyes.

Fluorescent Probes for Ecto-5'-nucleotidase (CD73).

Ecto-5'-nucleotidase (CD73) catalyzes the hydrolysis of AMP to anti-inflammatory, immunosuppressive adenosine. It is expressed on vascular endothelial, epithelial, and also numerous cancer cells where it strongly contributes to an immunosuppressive microenvironment. In the present study we designed and synthesized fluorescent-labeled CD73 inhibitors with low nanomolar affinity and high selectivity based on benzyl-α,β-methylene-ADP (PSB-12379) as a lead structure.

2-Substituted α,β-Methylene-ADP Derivatives: Potent Competitive Ecto-5'-nucleotidase (CD73) Inhibitors with Variable Binding Modes.

CD73 inhibitors are promising drugs for the (immuno)therapy of cancer. Here, we present the synthesis, structure-activity relationships, and cocrystal structures of novel derivatives of the competitive CD73 inhibitor α,β-methylene-ADP (AOPCP) substituted in the 2-position. Small polar or lipophilic residues increased potency, 2-iodo- and 2-chloro-adenosine-5'--[(phosphonomethyl)phosphonic acid] (, ) being the most potent inhibitors with values toward human CD73 of 3-6 nM.