9sme

Crystal structure of CD73 in complex with JMS04-14, a pyrimidine-based nucleoside bisphosphonate inhibitor, in the closed state and in crystal form III

spinqualitylabelsall models 9sme, resolution 2.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9sme is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.55Å Ligands: A1JOZ, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease 5NTD_HUMAN Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function 5NTD_HUMAN Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities. Publication Abstract from PubMed 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(i) values of ca. 1 nM) and favorable pharmacokinetic properties, yielding [(18)F]PSB-19427 ([(18)F]1) and [(18)F]MRS-4648 ([(18)F]2). Ex vivo imaging studies on human breast cancer tissues indicated specific binding of both radiotracers. Subsequent in vivo studies proved [(18)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 [(18)F]FDG, [(18)F]1 was superior in visualizing TNBC, offering potential advantages over [(18)F]FDG in terms of specificity and diagnostic accuracy. Thus, [(18)F]1 is a PET tracer with outstanding properties suitable for broad application in cancer diagnosis and personalized medicine. Fluorine-18-Labeled Nucleotide Analogs Targeting Ecto-5'-Nucleotidase (CD73) for Positron Emission Tomography Imaging of Solid Tumors.,Dobelmann C, Schmies CC, Rolshoven GW, Scortichini M, Wagner S, Isaak A, Idris RM, Dabel J, Grey L, Losenkova K, Moschutz S, Hroub HA, Keim A, Hoppner S, Sandholm J, Bostrom P, Hollmen M, Strater N, Hermann S, Yegutkin GG, Jacobson KA, Schelhaas S, Muller CE, Junker A Angew Chem Int Ed Engl. 2026 Apr 20;65(17):e22758. doi: 10.1002/anie.202522758. , Epub 2026 Mar 15. PMID:41834421 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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