ArticleProgress in biophysics and molecular biology2021
Fragment- and structure-based drug discovery for developing therapeutic agents targeting the DNA Damage Response.
Article in Progress in biophysics and molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Orchestrated metal ion repositioning defines the dynamic catalytic strategy of the essential DNA repair nuclease APE1.bioRxiv : the preprint server for biology · 2026Article
- Computational Innovations in Cancer Research and How Computing is Transforming Drug Discovery and Development: A Review.Mini reviews in medicinal chemistry · 2026Review
- Combining Cryo-EM with Computational Approaches To Revolutionize Structural Biology.The protein journal · 2025Review
- Treatment of Parkinson's Disease with an Anti-Inflammasome NLRP3 Inhibitor Derived from a Natural Product.ACS pharmacology & translational science · 2025Article
- Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy.Nucleic acids research · 2025Article
- Genome-wide pan-GPCR cell libraries accelerate drug discovery.Acta pharmaceutica Sinica. B · 2024Review
- AP endonuclease 1: Biological updates and advances in activity analysis.Methods in enzymology · 2024Article
- A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions.Frontiers in molecular biosciences · 2024Article
- A New Drug Discovery Platform: Application to DNA Polymerase Eta and Apurinic/Apyrimidinic Endonuclease 1.International journal of molecular sciences · 2023Article
- Article
- Advancements in small molecule drug design: A structural perspective.Drug discovery today · 2023Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Two-Step Validation Approach for Tools To Study the DNA Repair Enzyme SNM1A.Chembiochem : a European journal of chemical biology · 2023Article
- Characterizing inhibitors of human AP endonuclease 1.PloS one · 2023Article
- Methods for the Discovery and Identification of Small Molecules Targeting Oxidative Stress-Related Protein-Protein Interactions: An Update.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Targeting SARS-CoV-2 Nsp3 macrodomain structure with insights from human poly(ADP-ribose) glycohydrolase (PARG) structures with inhibitors.Progress in biophysics and molecular biology · 2021Article
- An effective human uracil-DNA glycosylase inhibitor targets the open pre-catalytic active site conformation.Progress in biophysics and molecular biology · 2021Article
- The renaissance in biophysics and molecular biology enabled by the interface of DNA repair and replication with cancer.Progress in biophysics and molecular biology · 2021Article
- Modeling DNA trapping of anticancer therapeutic targets using missense mutations identifies dominant synthetic lethal interactions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Cancer will directly affect the lives of over one-third of the population. The DNA Damage Response (DDR) is an intricate system involving damage recognition, cell cycle regulation, DNA repair, and ultimately cell fate determination, playing a central role in cancer etiology and therapy. Two primary therapeutic approaches involving DDR targeting include: combinatorial treatments employing anticancer genotoxic agents; and synthetic lethality, exploiting a sporadic DDR defect as a mechanism for cancer-specific therapy. Whereas, many DDR proteins have proven "undruggable", Fragment- and Structure-Based Drug Discovery (FBDD, SBDD) have advanced therapeutic agent identification and development. FBDD has led to 4 (with ∼50 more drugs under preclinical and clinical development), while SBDD is estimated to have contributed to the development of >200, FDA-approved medicines. Protein X-ray crystallography-based fragment library screening, especially for elusive or "undruggable" targets, allows for simultaneous generation of hits plus details of protein-ligand interactions and binding sites (orthosteric or allosteric) that inform chemical tractability, downstream biology, and intellectual property. Using a novel high-throughput crystallography-based fragment library screening platform, we screened five diverse proteins, yielding hit rates of ∼2-8% and crystal structures from ∼1.8 to 3.2 Å. We consider current FBDD/SBDD methods and some exemplary results of efforts to design inhibitors against the DDR nucleases meiotic recombination 11 (MRE11, a.k.a., MRE11A), apurinic/apyrimidinic endonuclease 1 (APE1, a.k.a., APEX1), and flap endonuclease 1 (FEN1).
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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.