ArticleBioorganic & medicinal chemistry letters2013
Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase.
Article in Bioorganic & medicinal chemistry letters, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Characterization and regulation of cell cycle-independent noncanonical gene targeting.Nature communications · 2024Article
- SMC5/6 Promotes Replication Fork Stability via Negative Regulation of the COP9 Signalosome.International journal of molecular sciences · 2024Article
- Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair.Frontiers in oncology · 2022Review
- The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance.Frontiers in immunology · 2022Article
- V-Dock: Fast Generation of Novel Drug-like Molecules Using Machine-Learning-Based Docking Score and Molecular Optimization.International journal of molecular sciences · 2021Article
- Exploiting DNA Damage Repair in Precision Cancer Therapy: BRCA1 as a Prime Therapeutic Target.Cancers · 2021Review
- Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein.eLife · 2021Article
- Synthetic Lethal Interactions of RECQ Helicases.Trends in cancer · 2021Review
- A high-throughput screen to identify novel small molecule inhibitors of the Werner Syndrome Helicase-Nuclease (WRN).PloS one · 2019Article
- New Insights Into DNA Helicases as Druggable Targets for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner.Oncotarget · 2017Article
- Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy.Cell chemical biology · 2017Review
- A Platform to Enable the Pharmacological Profiling of Small Molecules in Gel-Based Electrophoretic Mobility Shift Assays.Journal of biomolecular screening · 2016Article
- BRCA2 and RAD51 promote double-strand break formation and cell death in response to gemcitabine.Molecular cancer therapeutics · 2014Article
- Targeting the homologous recombination pathway by small molecule modulators.Bioorganic & medicinal chemistry letters · 2014Review
- RECQL1 and WRN DNA repair helicases: potential therapeutic targets and proliferative markers against cancers.Frontiers in genetics · 2014Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chemistry optimization of the hit molecule following a quantitative high-throughput screen of >355,000 compounds. These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome.
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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.