ArticleNature chemical biology2024
Discovery of VH domains that allosterically inhibit ENPP1.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Reliable Determination of ATP and Its Metabolites by LC-MS Using Blood Collection Tubes with and without Ectonucleotidase Inhibitors.ACS pharmacology & translational science · 2025Article
- cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025Review
- Review
- Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome.Chemical reviews · 2025Review
- ENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Targeting chromosomal instability in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- The balance of STING signaling orchestrates immunity in cancer.Nature immunology · 2024Review
- Surface and Global Proteome Analyses Identify ENPP1 and Other Surface Proteins as Actionable Immunotherapeutic Targets in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- From mechanism to therapy: the journey of CD24 in cancer.Frontiers in immunology · 2024Review
- Advancements in ovarian cancer immunodiagnostics and therapeutics via phage display technology.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Ectodomain phosphatase/phosphodiesterase-1 (ENPP1) is overexpressed on cancer cells and functions as an innate immune checkpoint by hydrolyzing extracellular cyclic guanosine monophosphate adenosine monophosphate (cGAMP). Biologic inhibitors have not yet been reported and could have substantial therapeutic advantages over current small molecules because they can be recombinantly engineered into multifunctional formats and immunotherapies. Here we used phage and yeast display coupled with in cellulo evolution to generate variable heavy (VH) single-domain antibodies against ENPP1 and discovered a VH domain that allosterically inhibited the hydrolysis of cGAMP and adenosine triphosphate (ATP). We solved a 3.2 Å-resolution cryo-electron microscopy structure for the VH inhibitor complexed with ENPP1 that confirmed its new allosteric binding pose. Finally, we engineered the VH domain into multispecific formats and immunotherapies, including a bispecific fusion with an anti-PD-L1 checkpoint inhibitor that showed potent cellular activity.
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What OpenQuestion holds
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.