ArticleJournal of molecular biology2015
Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL.
Article in Journal of molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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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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
29 citing papers in PubMed, 40 citations in OpenAlex.
- Computational design of potent and selective binders of BAK and BAX.Science advances · 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
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia.Haematologica · 2025Article
- Modeling the Binding of Anticancer Peptides and Mcl-1.International journal of molecular sciences · 2024Article
- Machine learning to predict continuous protein properties from binary cell sorting data and map unseen sequence space.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Peptides from human BNIP5 and PXT1 and non-native binders of pro-apoptotic BAK can directly activate or inhibit BAK-mediated membrane permeabilization.Structure (London, England : 1993) · 2023Article
- Rational design of Harakiri (HRK)-derived constrained peptides as BCL-xChemical communications (Cambridge, England) · 2023Article
- Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Design of Protein Segments and Peptides for Binding to Protein Targets.Biodesign research · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Rational Design of Peptide-Based Inhibitors Disrupting Protein-Protein Interactions.Frontiers in chemistry · 2021Review
- Genetically Encoded Fluorescent Biosensor for Rapid Detection of Protein Expression.ACS synthetic biology · 2020Article
- Specific interactions of BCL-2 family proteins mediate sensitivity to BH3-mimetics in diffuse large B-cell lymphoma.Haematologica · 2020Article
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Quantitative mapping of binding specificity landscapes for homologous targets by using a high-throughput method.The Biochemical journal · 2020Article
- BH3 profiling discriminates the anti‑apoptotic status of 5‑fluorouracil‑resistant colon cancer cells.Oncology reports · 2019Article
- Molecular evolution of peptides by yeast surface display technology.MedChemComm · 2019Review
- Peptide design by optimization on a data-parameterized protein interaction landscape.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies.JCI insight · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Bcl-2 family of proteins plays a critical role regulating apoptosis, and pro-survival Bcl-2 family members are important therapeutic targets due to their overexpression in different cancers. Pro-apoptotic Bcl-2 homology 3 (BH3)-only proteins antagonize pro-survival Bcl-2 protein functions by binding directly to them, and a sub-class of BH3-only proteins termed sensitizers can initiate apoptosis via this mechanism in response to diverse signals. The five pro-survival proteins Bcl-xL, Mcl-1, Bcl-2, Bcl-w and Bfl-1 differ in their binding preferences, with Bcl-xL, Bcl-2 and Bcl-w sharing similar interaction profiles for many natural sensitizers and small molecules. Peptides that bind selectively to just one or a subset of family members have shown utility in assays that diagnose apoptotic blockades in cancer cells and as reagents for dissecting apoptotic mechanism. Combining computational design, combinatorial library screening and rational mutagenesis, we designed a series of BH3 sensitizer peptides that bind Bcl-xL with sub-nanomolar affinity and selectivity up to 1000-fold over each of the four competing pro-survival proteins. We demonstrate the efficacy of our designed BH3 peptides in assays that differentiate between cancer cells that are dependent on different pro-survival proteins.
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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.