ArticleThe Journal of clinical investigation2012
A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 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
112 citing papers in PubMed, 173 citations in OpenAlex.
- Serum level of miR-10-5p as a prognostic biomarker for acute myeloid leukemia.International journal of hematology · 2015Trial
- Targeting LKB1-inactivated lung cancers with a stapled peptide inhibitor of the CRTC-CREB pathway.Molecular therapy. Oncology · 2026Article
- Disarming the Hsp70-Bim Alliance: Small-Molecule and Peptidic Disruptors of a Chaperone-Apoptotic Switch in Cancer.ChemistryOpen · 2026Review
- A triple-action PROTAC for wild-type p53 cancer therapy.Cell reports. Medicine · 2025Article
- Expanding the Chemical Space of Mechanically Interlocked Peptides (MIPs) via Rational Design and Metabolite Profiling.JACS Au · 2025Article
- Structural insights into chemoresistance mutants of BCL-2 and their targeting by stapled BAD BH3 helices.Nature communications · 2025Article
- Molecular mechanisms underlying HRK interaction with BCL-XL and BCL-2 reveal specificity determinants for BH3 mimetics.iScience · 2025Article
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Inhibitory Potential and Binding Thermodynamics of Scyllatoxin-Based BH3 Domain Mimetics Targeting Repressor BCL2 Proteins.Journal of molecular recognition : JMR · 2025Article
- Chemoselective, regioselective, and positionally selective fluorogenic stapling of unprotected peptides for cellular uptake and direct cell imaging.Chemical science · 2025Article
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Cancer-Targeting Applications of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- The Role of Structural Flexibility in Hydrocarbon-Stapled Peptides Designed to Block Viral Infection via Human ACE2 Mimicry.Peptide science (Hoboken, N.J.) · 2024Article
- Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XNature communications · 2024Article
- Article
- Cancer Cell Membrane Wrapped Nanoparticles for the Delivery of a Bcl-2 Inhibitor to Triple-Negative Breast Cancer.Molecular pharmaceutics · 2023Article
- Strategies to improve the physicochemical properties of peptide-based drugs.Pharmaceutical research · 2023Review
- A novel Mcl-1 inhibitor synergizes with venetoclax to induce apoptosis in cancer cells.Molecular medicine (Cambridge, Mass.) · 2023Article
- Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Harnessing the Therapeutic Potential of Biomacromolecules through Intracellular Delivery of Nucleic Acids, Peptides, and Proteins.Advanced healthcare materials · 2022Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2-interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence-specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death.
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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.