ArticleOncoTargets and therapy2021
A Novel CD73 Inhibitor SHR170008 Suppresses Adenosine in Tumor and Enhances Anti-Tumor Activity with PD-1 Blockade in a Mouse Model of Breast Cancer.
Article in OncoTargets and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Metabolic immune checkpoints in cancer: how tumor-derived metabolites shape immunotherapy resistance.Frontiers in immunology · 2026Review
- Article
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- Development of CD73 Inhibitors in Tumor Immunotherapy and Opportunities in Imaging and Combination Therapy.Journal of medicinal chemistry · 2025Review
- Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review.Purinergic signalling · 2025Review
- Enzymatic and microenvironmental regulation in adenosine metabolism-mediated immunosuppression.Frontiers in immunology · 2025Review
- Clinical application of PBMCs in breast cancer: detection, treatment evaluation and prognosis.Frontiers in cell and developmental biology · 2025Review
- The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.Acta pharmaceutica Sinica. B · 2024Review
- CD73: agent development potential and its application in diabetes and atherosclerosis.Frontiers in immunology · 2024Review
- Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
- The Clinical Significance of CD73 in Cancer.International journal of molecular sciences · 2023Review
- Is the regulation by miRNAs of NTPDase1 and ecto-5'-nucleotidase genes involved with the different profiles of breast cancer subtypes?Purinergic signalling · 2022Article
- Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy.Frontiers in immunology · 2022Review
- Emerging Therapeutic Strategies of Different Immunotherapy Approaches Combined with PD-1/PD-L1 Blockade in Cervical Cancer.Drug design, development and therapy · 2022Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cells, and promote anti-PD-1 mAb therapy-induced immune escape. Consequently, developing a CD73 inhibitor as monotherapy and a potential beneficial combination partner with immune-checkpoint inhibitors needs investigation.
methodsCD73 inhibitors were evaluated in vitro with soluble and membrane-bound CD73 enzymes, as well as its PD biomarker responses in human peripheral blood mononuclear cells (PBMC) by flow cytometry and ELISA. The binding modes of the molecules were analyzed via molecular modeling. The anti-tumor activity and synergistic effect of SHR170008 in combination with anti-PD-1 mAb were evaluated in a syngeneic mouse breast cancer model.
resultsSHR170008 was discovered during the initial structural modifications on the link between the ribose and the α-phosphate of AMPCP, which significantly improved the stability of the compound confirmed by the metabolite identification study. Further modifications on the adenine base of AMPCP improved the potency due to forming stronger interactions with CD73 protein. It exhibited potent inhibitory activities on soluble and endogenous membrane-bound CD73 enzymes, and induced IFNγ production, reversed AMP-suppressed CD25
conclusionOur findings suggest that CD73 may serve as an immune checkpoint by generating adenosine, which suppresses the antitumor activity of anti-PD-1 mAb, and inhibition of CD73 may be a potential beneficial combination partner with immune-checkpoint inhibitors to improve their therapeutic outcomes in general.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.