ArticleCancer research2013
Novel small-molecule inhibitors of Bcl-XL to treat lung cancer.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
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- Mitochondria of T Lymphocytes Promote Anti-Pulmonary Tumor Immune Response.World journal of oncology · 2024Article
- Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.Life science alliance · 2024Article
- The inhibition of Beclin1-dependent autophagy sensitizes PTC cells to ABT737-induced death.Genetics and molecular biology · 2024Article
- DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining.Nucleic acids research · 2023Article
- CYD0281, a Bcl-2 BH4 domain antagonist, inhibits tumor angiogenesis and breast cancer tumor growth.BMC cancer · 2023Article
- B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease.Exploration of targeted anti-tumor therapy · 2023Review
- Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.Frontiers in immunology · 2023Review
- Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells.Science advances · 2022Article
- ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model.Yonsei medical journal · 2022Article
- Discovery of Small Molecule Bak Activator for Lung Cancer Therapy.Theranostics · 2021Article
- Targeting apoptosis in cancer therapy.Nature reviews. Clinical oncology · 2020Review
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- Mcl-1 Interacts with Akt to Promote Lung Cancer Progression.Cancer research · 2019Article
- A low-molecular-weight compound exerts anticancer activity against breast and lung cancers by disrupting EGFR/Eps8 complex formation.Journal of experimental & clinical cancer research : CR · 2019Article
- Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy.Molecular cancer · 2019Article
- Antigen-specific primed cytotoxic T cells eliminate tumour cells in vivo and prevent tumour development, regardless of the presence of anti-apoptotic mutations conferring drug resistance.Cell death and differentiation · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Bcl-XL is a major antiapoptotic protein in the Bcl-2 family whose overexpression is more widely observed in human lung cancer cells than that of Bcl-2, suggesting that Bcl-XL is more biologically relevant and therefore a better therapeutic target for lung cancer. Here, we screened small molecules that selectively target the BH3 domain (aa 90-98) binding pocket of Bcl-XL using the UCSF DOCK 6.1 program suite and the NCI chemical library database. We identified two new Bcl-XL inhibitors (BXI-61 and BXI-72) that exhibit selective toxicity against lung cancer cells compared with normal human bronchial epithelial cells. Fluorescence polarization assay reveals that BXI-61 and BXI-72 preferentially bind to Bcl-XL protein but not Bcl2, Bcl-w, Bfl-1/A1, or Mcl-1 in vitro with high binding affinities. Treatment of cells with BXI-72 results in disruption of Bcl-XL/Bak or Bcl-XL/Bax interaction, oligomerization of Bak, and cytochrome c release from mitochondria. Importantly, BXI-61 and BXI-72 exhibit more potent efficacy against human lung cancer than ABT-737 but less degree in platelet reduction in vivo. BXI-72 overcomes acquired radioresistance of lung cancer. On the basis of our findings, the development of BXI(s) as a new class of anticancer agents is warranted and represents a novel strategy for improving lung cancer outcome.
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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.