ArticleCell chemical biology2016
Selective Covalent Targeting of Anti-Apoptotic BFL-1 by Cysteine-Reactive Stapled Peptide Inhibitors.
Article in Cell chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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.
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Who cites it
42 citing papers in PubMed, 80 citations in OpenAlex.
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- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Folded-state compatibility and unfolded-state constraint govern staple-based stabilization: guidelines from a coiled-coil model.RSC chemical biology · 2026Article
- Protein structural dynamics in covalent drug design: insights from irreversible and reversible covalent inhibitors.RSC chemical biology · 2026Review
- The use of venetoclax in the treatment of acute lymphoblastic leukemia-a systematic review.Therapeutic advances in medical oncology · 2026Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Structural insights into chemoresistance mutants of BCL-2 and their targeting by stapled BAD BH3 helices.Nature communications · 2025Article
- Understanding the Functional Dependence and Inhibition of the Bcl‑2 Pro-Survival Proteins in a Wide Spectrum of Cancers toward Precision Medicine.ACS pharmacology & translational science · 2025Article
- Targeted Penetrating Motif Engineering of BH3 Mimetic: Harnessing Non-Canonical Amino Acids for Coinhibition of MCL-1 and BCL-xL in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rational Design of Stapled Covalent Peptide Modifiers of Oncoprotein E6 from Human Papillomavirus.ACS chemical biology · 2025Article
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Discovering covalent cyclic peptide inhibitors of peptidyl arginine deiminase 4 (PADI4) using mRNA-display with a genetically encoded electrophilic warhead.Communications chemistry · 2024Article
- Identification and Evaluation of Reversible Covalent Binders to Cys55 of Bfl-1 from a DNA-Encoded Chemical Library Screen.ACS medicinal chemistry letters · 2024Article
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- Peptide-based covalent inhibitors of protein-protein interactions.Journal of peptide science : an official publication of the European Peptide Society · 2023Review
- Recent applications of covalent chemistries in protein-protein interaction inhibitors.RSC medicinal chemistry · 2022Review
- Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer.Biochemical Society transactions · 2021Review
- Covalent and Noncovalent Targeting of the Tcf4/β-Catenin Strand Interface with β-Hairpin Mimics.ACS chemical biology · 2021Article
- Covalent flexible peptide docking in Rosetta.Chemical science · 2021Article
- Targeting Bfl-1 via acute CDK9 inhibition overcomes intrinsic BH3-mimetic resistance in lymphomas.Blood · 2021Article
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5 authors at 1 institution in 1 country.
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Abstract
Anti-apoptotic BCL-2 family proteins block cell death by trapping the critical α-helical BH3 domains of pro-apoptotic members in a surface groove. Cancer cells hijack this survival mechanism by overexpressing a spectrum of anti-apoptotic members, mounting formidable apoptotic blockades that resist chemotherapeutic treatment. Drugging the BH3-binding pockets of anti-apoptotic proteins has become a highest-priority goal, fueled by the clinical success of ABT-199, a selective BCL-2 inhibitor, in reactivating apoptosis in BCL-2-dependent cancers. BFL-1 is a BCL-2 homolog implicated in melanoma, lymphoma, and other cancers, and remains undrugged. A natural juxtaposition of two unique cysteines at the binding interface of the NOXA BH3 helix and BFL-1 pocket informed the development of stapled BH3 peptides bearing acrylamide warheads to irreversibly inhibit BFL-1 by covalent targeting. Given the frequent proximity of native cysteines to regulatory binding surfaces, covalent stapled peptide inhibitors provide a new therapeutic strategy for targeting pathologic protein interactions.
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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.