ArticleJournal of medicinal chemistry2018
Discovery of Potent 2-Aryl-6,7-dihydro-5 H-pyrrolo[1,2- a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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
34 citing papers in PubMed, 67 citations in OpenAlex.
- Decoding WDR5-Mediated Interactions in Gliomas: Implications for Targeted Therapy.Medicinal research reviews · 2026Review
- An electron-density point-cloud framework for robust protein-ligand interaction prediction.Nature communications · 2026Article
- Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Crystal structures of Kif2A complexed with WDR5 reveal the structural plasticity of WIN-S7 sites.Acta biochimica et biophysica Sinica · 2025Article
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Article
- Ribosome subunit attrition and activation of the p53-MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition.bioRxiv : the preprint server for biology · 2024Article
- Structure-Based Discovery of Potent, Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors.Journal of medicinal chemistry · 2023Article
- Discovery of Potent and Selective WDR5 Proteolysis Targeting Chimeras as Potential Therapeutics for Pancreatic Cancer.Journal of medicinal chemistry · 2023Article
- Recent Progress in Modulation of WD40-Repeat Domain 5 Protein (WDR5): Inhibitors and Degraders.Cancers · 2023Review
- Discovery, evaluation and mechanism study of WDR5-targeted small molecular inhibitors for neuroblastoma.Acta pharmacologica Sinica · 2023Article
- Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Exiting the tunnel of uncertainty: crystal soak to validated hit.Acta crystallographica. Section D, Structural biology · 2022Article
- Cosolvent Simulations with Fragment-Bound Proteins Identify Hot Spots to Direct Lead Growth.Journal of chemical theory and computation · 2022Article
- Article
- Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization.Journal of medicinal chemistry · 2022Article
- Lysine methyltransferase inhibitors: where we are now.RSC chemical biology · 2022Review
- Article
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
WDR5 is a chromatin-regulatory scaffold protein overexpressed in various cancers and a potential epigenetic drug target for the treatment of mixed-lineage leukemia. Here, we describe the discovery of potent and selective WDR5-WIN-site inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified several chemically distinct hit series that bind to the WIN site within WDR5. Members of a 6,7-dihydro-5 H-pyrrolo[1,2- a]imidazole fragment class were expanded using a structure-based design approach to arrive at lead compounds with dissociation constants <10 nM and micromolar cellular activity against an AML-leukemia cell line. These compounds represent starting points for the discovery of clinically useful WDR5 inhibitors for the treatment of cancer.
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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.