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
This is a non-PDB format compatible entry.
Summary for 9SME
| Entry DOI | 10.2210/pdb9sme/pdb |
| Descriptor | 5'-nucleotidase, ZINC ION, [[(2~{R},3~{S},4~{R},5~{R})-5-[(4~{E})-3-methyl-2-oxidanylidene-4-phenylmethoxyimino-pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]methylphosphonic acid, ... (4 entities in total) |
| Functional Keywords | ecto-5'-nucleotidase, zinc enzyme, dimetal center, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 120062.48 |
| Authors | Strater, N.,Junker, A.,Muller, C.E.,Moschuetz, S. (deposition date: 2025-09-07, release 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 Cited by 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: 41834421DOI: 10.1002/anie.202522758 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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