ArticleOncotarget2015
A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- CYD0281, a Bcl-2 BH4 domain antagonist, inhibits tumor angiogenesis and breast cancer tumor growth.BMC cancer · 2023Article
- Novel BH4-BCL-2 Domain Antagonists Induce BCL-2-Mediated Apoptosis in Triple-Negative Breast Cancer.Cancers · 2022Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles.International journal of molecular sciences · 2021Review
- Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma.Cells · 2021Review
- Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells.International journal of molecular sciences · 2021Article
- BDA-366, a putative Bcl-2 BH4 domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models.Cell death & disease · 2020Article
- BDA-366, a putative Bcl-2 BH4 domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models.Cell death & disease · 2020Article
- Lessons from the Endoplasmic Reticulum CaCells · 2020Review
- Bcl-2-Protein Family as Modulators of IPCold Spring Harbor perspectives in biology · 2020Review
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- Creating a New Cancer Therapeutic Agent by Targeting the Interaction between Bcl-2 and IPCold Spring Harbor perspectives in biology · 2019Review
- Constitutive IPCell death and differentiation · 2019Article
- Recent advances in uncovering the mechanisms contributing to BIRD-2-induced cell death in B-cell cancer cells.Cell death & disease · 2019Article
- Targeting Bcl-2-IPBiochimica et biophysica acta. Molecular cell research · 2018Review
- BH4-mimetics and -antagonists: an emerging class of Bcl-2 protein modulators for cancer therapy.Oncotarget · 2018Article
- The mitochondrial pathway is involved in sodium fluoride (NaF)-induced renal apoptosis in mice.Toxicology research · 2018Article
- Integration of CaOncogene · 2018Article
- Emerging molecular mechanisms in chemotherapy: CaCell death & disease · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP3Rs), inhibiting pro-apoptotic Ca2+ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP3R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton's tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP3R interaction.
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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.