ArticleCell chemical biology2023
Structurally distinct PARP7 inhibitors provide new insights into the function of PARP7 in regulating nucleic acid-sensing and IFN-β signaling.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma.Oncoimmunology · 2026Article
- PARP7 inhibitors enhance the immunogenic effects of radiation in pancreatic cancer cells.Molecular therapy. Oncology · 2026Article
- Structure, function, regulation, evolution, and therapeutic implications of PARP14.Genes & development · 2026Review
- PARP7 protects the lung epithelial barrier from diverse environmental threats.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NADCell reports · 2026Article
- Ubiquitin pathway blockade reveals endogenous ADP-ribosylation marking PARP7 and AHR for degradation.The EMBO journal · 2026Article
- PARP7 and aryl hydrocarbon receptor differentially regulate mammary cancer cell proliferation and STING-induced type I interferon signalling.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Targeting MARylation and DePARylation in Cancer Therapy: New Promising Therapeutic Opportunities.Cancers · 2025Review
- PARP7 is a proteotoxic stress sensor that labels proteins for degradation.The EMBO journal · 2025Article
- PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice.Cell reports · 2025Article
- Mono-ADP-ribosylating PARP enzymes in cellular signaling and disease.Journal of cell science · 2025Review
- PARP7 inhibits type I interferon signaling to prevent autoimmunity and lung disease.The Journal of experimental medicine · 2025Article
- PARP7 as a new target for activating anti-tumor immunity in cancer.EMBO molecular medicine · 2025Review
- RACK1 MARylation regulates translation and stress granules in ovarian cancer cells.The Journal of cell biology · 2025Article
- Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- A multilineage screen identifies actionable synthetic lethal interactions in human cancers.Nature genetics · 2025Article
- Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.Current pharmaceutical biotechnology · 2025Review
- Pathological and physiological roles of ADP-ribosylation: established functions and new insights.Biological chemistry · 2024Review
- Loss ofFrontiers in immunology · 2024Article
- PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
The mono-ADP-ribosyltransferase PARP7 has emerged as a key negative regulator of cytosolic NA-sensors of the innate immune system. We apply a rational design strategy for converting a pan-PARP inhibitor into a potent selective PARP7 inhibitor (KMR-206). Consistent with studies using the structurally distinct PARP7 inhibitor RBN-2397, co-treatment of mouse embryonic fibroblasts with KMR-206 and NA-sensor ligands synergistically induced the expression of the type I interferon, IFN-β. In mouse colon carcinoma (CT-26) cells, KMR-206 alone induced IFN-β. Both KMR-206 and RBN-2397 increased PARP7 protein levels in CT-26 cells, demonstrating that PARP7's catalytic activity regulates its own protein levels. Curiously, treatment with saturating doses of KMR-206 and RBN-2397 achieved different levels of PARP7 protein, which correlated with the magnitude of type I interferon gene expression. These latter results have important implications for the mechanism of action of PARP7 inhibitors and highlights the usefulness of having structurally distinct chemical probes for the same target.
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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.