9HD5

Crystal structure of CD73 (ecto-5'-nucleotidase) in complex with the AOPCP derivative PSB19427 in the closed state

This is a non-PDB format compatible entry.

Summary for 9HD5

• Entry DOI: 10.2210/pdb9hd5/pdb
• Descriptor: 5'-nucleotidase, ZINC ION, [[(2~{R},3~{S},4~{R},5~{R})-5-[2-chloranyl-6-[[4-[1-(2-fluoranylethyl)-1,2,3-triazol-4-yl]phenyl]methyl-propyl-amino]purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]methylphosphonic acid, ... (4 entities in total)
• Functional Keywords: ecto-5-nucleotidase, amp hydrolysis, inhibition, pet tracer, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 121397.60

Authors

Strater, N.,Moschuetz, S.,Dobelmann, C.,Schmies, C.C.,Jacobson, K.A.,Muller, C.E.,Junker, A. (deposition date: 2024-11-11, release date: 2025-11-19, Last modification date: 2026-08-12)

Primary citation

Dobelmann, C.,Schmies, C.C.,Rolshoven, G.W.,Scortichini, M.,Wagner, S.,Isaak, A.,Idris, R.M.,Dabel, J.,Grey, L.,Losenkova, K.,Moschutz, S.,Hroub, H.A.,Keim, A.,Hoppner, S.,Sandholm, J.,Bostrom, P.,Hollmen, M.,Strater, N.,Hermann, S.,Yegutkin, G.G.,Jacobson, K.A.,Schelhaas, S.,Muller, C.E.,Junker, A.
Fluorine-18-Labeled Nucleotide Analogs Targeting Ecto-5'-Nucleotidase (CD73) for Positron Emission Tomography Imaging of Solid Tumors.
Angew.Chem.Int.Ed.Engl., 65:e22758-e22758, 2026

PubMed Abstract: Ecto-5'-nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression is associated with various aggressive cancers, including triple-negative breast cancer (TNBC) and pancreatic cancer, making it a promising target for diagnostic imaging. Besides antibodies, small-molecule CD73 inhibitors have been developed and are currently in clinical trials. This study aimed to develop and evaluate fluorine-18 labeled high-affinity CD73 inhibitors as tracers for the non-invasive positron emission tomography (PET) imaging of CD73 expression in cancer. Two CD73 inhibitors were selected for radiolabeling based on their high potency (K values of ca. 1 nM) and favorable pharmacokinetic properties, yielding [F]PSB-19427 ([F]1) and [F]MRS-4648 ([F]2). Ex vivo imaging studies on human breast cancer tissues indicated specific binding of both radiotracers. Subsequent in vivo studies proved [F]1 to be superior due to its long elimination half-life and its accumulation in TNBC and pancreatic cancer tissues, suggesting its potential as a versatile PET tracer for imaging of various solid tumors. Compared to [F]FDG, [F]1 was superior in visualizing TNBC, offering potential advantages over [F]FDG in terms of specificity and diagnostic accuracy. Thus, [F]1 is a PET tracer with outstanding properties suitable for broad application in cancer diagnosis and personalized medicine.

PubMed: 41834421
DOI: 10.1002/anie.202522758

Experimental method

X-RAY DIFFRACTION (2.911 Å)