ArticleCell chemical biology2020
Development and Characterization of a Wee1 Kinase Degrader.
Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Targeting WEE1 kinase: an integrated machine learning-cheminformatics framework for ultra-large-scale virtual screening and novel inhibitor discovery.Journal of computer-aided molecular design · 2026Article
- Computational mapping of productive POI-E3 ligase conformations to guide de novo degrader design: application to WEE1 and PKMYT1 PROTACs.Journal of cheminformatics · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1.Asian journal of pharmaceutical sciences · 2026Review
- WEE1 kinase in cancer: Molecular mechanisms and inhibitor insights.EXCLI journal · 2026Review
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Review
- Deubiquitinase-Targeting Chimeras (DUBTACs) as a Potential Paradigm-Shifting Drug Discovery Approach.Journal of medicinal chemistry · 2025Review
- Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).Journal of medicinal chemistry · 2025Article
- Navigating PROTACs in Cancer Therapy: Advancements, Challenges, and Future Horizons.Food science & nutrition · 2025Review
- Latest Advancements of Natural Products in Combating Ovarian Cancer.Journal of Cancer · 2025Review
- Matrix stiffness influences drug resistance to gemcitabine analog and AZD 1775 combination in PDAC organoids.PloS one · 2025Article
- Discovery of CRBN-Dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library.Journal of the American Chemical Society · 2024Article
- Discovery of electrophilic degraders that exploit SbioRxiv : the preprint server for biology · 2024Article
- Targeted kinase degradation via the KLHDC2 ubiquitin E3 ligase.Cell chemical biology · 2023Article
- Autophagy modulates the stability of Wee1 and cell cycle G2/M transition.Biochemical and biophysical research communications · 2023Article
- Development and Characterization of Selective FAK Inhibitors and PROTACs with In Vivo Activity.Chembiochem : a European journal of chemical biology · 2023Article
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13 authors.
Funding
Abstract
The G1/S cell cycle checkpoint is frequently dysregulated in cancer, leaving cancer cells reliant on a functional G2/M checkpoint to prevent excessive DNA damage. Wee1 regulates the G2/M checkpoint by phosphorylating CDK1 at Tyr15 to prevent mitotic entry. Previous drug development efforts targeting Wee1 resulted in the clinical-grade inhibitor, AZD1775. However, AZD1775 is burdened by dose-limiting adverse events, and has off-target PLK1 activity. In an attempt to overcome these limitations, we developed Wee1 degraders by conjugating AZD1775 to the cereblon (CRBN)-binding ligand, pomalidomide. The resulting lead compound, ZNL-02-096, degrades Wee1 while sparing PLK1, induces G2/M accumulation at 10-fold lower doses than AZD1775, and synergizes with Olaparib in ovarian cancer cells. We demonstrate that ZNL-02-096 has CRBN-dependent pharmacology that is distinct from AZD1775, which justifies further evaluation of selective Wee1 degraders.
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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.