ArticleACS chemical biology2017
Discovery of a Selective Allosteric Inhibitor Targeting Macrodomain 2 of Polyadenosine-Diphosphate-Ribose Polymerase 14.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Structure, function, regulation, evolution, and therapeutic implications of PARP14.Genes & development · 2026Review
- Derivatives of MOPS: promising scaffolds for SARS coronaviruses Macro domain-targeted inhibition.The FEBS journal · 2025Article
- Mutation of a highly conserved isoleucine residue in loop 2 of several β-coronavirus macrodomains indicates that enhanced ADP-ribose binding is detrimental for replication.Journal of virology · 2024Article
- Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Mutation of a highly conserved isoleucine residue in loop 2 of severalbioRxiv : the preprint server for biology · 2024Article
- Crystal structure and biochemical activity of the macrodomain from rubella virus p150.Journal of virology · 2024Article
- A small-molecule inhibitor of TopBP1 exerts anti-MYC activity and synergy with PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities.Science advances · 2023Article
- Updated protein domain annotation of the PARP protein family sheds new light on biological function.Nucleic acids research · 2023Article
- Privileged Scaffolds for Potent and Specific Inhibitors of Mono-ADP-Ribosylating PARPs.Molecules (Basel, Switzerland) · 2023Review
- Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors.Pathogens (Basel, Switzerland) · 2023Article
- Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain.Bioorganic & medicinal chemistry · 2022Article
- Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2.bioRxiv : the preprint server for biology · 2022Article
- Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening.Antiviral research · 2022Article
- Medicinal Chemistry Perspective on Targeting Mono-ADP-Ribosylating PARPs with Small Molecules.Journal of medicinal chemistry · 2022Review
- Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.Journal of hematology & oncology · 2022Review
- The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses.Pathogens (Basel, Switzerland) · 2022Article
- A molecular toolbox for ADP-ribosyl binding proteins.Cell reports methods · 2021Article
- Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.Science advances · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Macrodomains are conserved protein interaction modules that can be found in all domains of life including in certain viruses. Macrodomains mediate recognition of sequence motifs harboring adenosine diphosphate ribose (ADPR) modifications, thereby regulating a variety of cellular processes. Due to their role in cancer or viral pathogenesis, macrodomains have emerged as potential therapeutic targets, but the unavailability of small molecule inhibitors has hampered target validation studies so far. Here, we describe an efficient screening strategy for identification of small molecule inhibitors that displace ADPR from macrodomains. We report the discovery and characterization of a macrodomain inhibitor, GeA-69, selectively targeting macrodomain 2 (MD2) of PARP14 with low micromolar affinity. Co-crystallization of a GeA-69 analogue with PARP14 MD2 revealed an allosteric binding mechanism explaining its selectivity over other human macrodomains. We show that GeA-69 engages PARP14 MD2 in intact cells and prevents its localization to sites of DNA damage.
Indexed as
Identifiers
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.