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  1. Oct 4, 2024Overexpression of the antiapoptotic protein B-cell lymphoma-extra large (BCL-X L) is associated with drug resistance and disease progression in numerous cancers.The compelling nature of this protein as a therapeutic target prompted efforts to develop selective small-molecule BCL-X L inhibitors. Although efficacious in preclinical models, we report herein that selective BCL-X L inhibitors cause ...
    • Efficacy and specificity of inhibitors of BCL-2 family ... - Science

      (A) Schematic representations of the human amino acid (aa) sequence for the analyzed BCL-2 family proteins (1-5). BH regions are indicated with numbers 1 to 4, with the BH3 region indicated in red; membrane-binding region types are specified.

    • BCL6 promotes a stem-like CD8 + T cell program in cancer via ... - Science

      Intratumoral exhausted CD8 + stem- or progenitor-like (T prog) and terminally differentiated (T term) cells mediate antitumor immunity and response to immunotherapy.Sun et al. investigated how exhausted CD8 + T cells are transcriptionally regulated in murine tumor models, identifying that the transcription factors BCL6 and BLIMP1 reciprocally regulate T prog and T term cell fates, respectively.

  2. pubmed.ncbi.nlm.nih.gov

    Oct 4, 2024Overexpression of the antiapoptotic protein B-cell lymphoma-extra large (BCL-X L) is associated with drug resistance and disease progression in numerous cancers.The compelling nature of this protein as a therapeutic target prompted efforts to develop selective small-molecule BCL-X L inhibitors. Although efficacious in preclinical models, we report herein that selective BCL-X L inhibitors cause ...
  3. pubmed.ncbi.nlm.nih.gov

    The BCL-2/BCL-XL/BCL-W inhibitor ABT-263 (navitoclax) has shown promising clinical activity in lymphoid malignancies such as chronic lymphocytic leukemia. However, its efficacy in these settings is limited by thrombocytopenia caused by BCL-XL inhibition. This prompted the generation of the BCL-2-sel …
    Author:Joel D. Leverson, Darren C. Phillips, Michael J. Mitten, Erwin R. Boghaert, Dolores Diaz, Stephen K....Published:2015
  4. Oct 20, 2023Intratumoral exhausted CD8 + stem- or progenitor-like (T prog) and terminally differentiated (T term) cells mediate antitumor immunity and response to immunotherapy.Sun et al. investigated how exhausted CD8 + T cells are transcriptionally regulated in murine tumor models, identifying that the transcription factors BCL6 and BLIMP1 reciprocally regulate T prog and T term cell fates, respectively.
  5. ncbi.nlm.nih.gov

    National Center for Biotechnology Information

    https://www.ncbi.nlm.nih.gov › pmc › articles › PMC4448555

    Dimerization of Bcl-xL. Oligomerization of Bcl-2 family of proteins is an essential step toward mitochondrial outer membrane insertion 21,22.Previously it was shown that Bcl-xL (ΔCT) when mixed with synthetic liposomes could be recovered as 3DDS dimer 21.The full-length Bcl-xL containing the long flexible loop (L) and the hydrophobic transmembrane C-terminal domain (CT) exhibits limited ...
  6. pubmed.ncbi.nlm.nih.gov

    Activated microglia/macrophages robustly expressed Bcl-x(L) 7 days after SCI, and a subpopulation showing nuclear condensation also expressed P-ser(62)-Bcl-x(L). Therefore, phosphorylation of Bcl-x(L) may have opposite effects in injured spinal cords: 1) it may decrease levels of the antiapoptotic Bcl-x(L) in neurons contributing to neuronal ...
  7. ashpublications.org

    Escape from apoptosis is a hallmark of malignant cells that constitute an important mechanism associated to therapeutic resistance. Hematologic malignant cells are described as primed for apoptosis, a state in which pro-survival BCL2 family proteins sequester elevated levels of pro-apoptotic BH3-only proteins or even pre-activated BAX/BAK to ensure survival.
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