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Mimetics bh3 mimetics
Bh3 Mimetics, supplied by Mimetics, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/bh3-mimetics/bh3+mimetics/pm42201388-430-3-4
Average 86 stars, based on 1 article reviews
bh3 mimetics - by Bioz Stars, 2026-09
86/100 stars

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Binding Assay:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Enzyme-linked Immunosorbent Assay:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Clone Assay:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Concentration Assay:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Incubation:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Flow Cytometry:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Standard Deviation:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Disruption:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Staining:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Imaging:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Immunofluorescence:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

CRISPR:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Knock-Out:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Sequencing:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Western Blot:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Two Tailed Test:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Purification:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Expressing:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].

Software:

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: In consequence TCA cycle is strongly downregulated that sensitive cells to BH3-mimetics.

Article Title: Activation of LXRβ Inhibits Tumor Respiration and is Synthetically Lethal with Bcl-xL Inhibition
Article Snippet: Major comments: *Figure 1G: The authors indicate that LXR ligands and BH3-mimetics "were chosen based on prior studies".

Article Title: Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia
Article Snippet: Alternative inhibitors of BTK, BTK degraders, novel BH3-mimetics, therapeutic antibodies towards tumor antigens and immune cell approaches such as bispecific antibodies and cellular therapies are being developed and studied.

Article Title:
Article Snippet: Table of Contents Appendix Figure S1: Enhanced apoptosis induction by the combination treatment of BH3- mimetics and LXR623.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: No signal was detected when BIM was deleted ( ) or complexes were disrupted with BH3-mimetics ( ).

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein-Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs.
Article Snippet: Ewald, L.; Dittmann, J.; Vogler, M.; Fulda, S. Side-by-Side Comparison of BH3-Mimetics Identifies MCL-1 as a Key Therapeutic Target in AML.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Moreover, identifying the specific protein complexes involved in survival reveals the cancer cell vulnerabilities and, therefore, guides the use of an appropriate class of BH3-mimetics whether alone or as part of a combination treatment.

Article Title: Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
Article Snippet: Additional BH3-mimetics that co-target BCL-2 and BCL-XL, MCL-1, or BCL-XL are in various stages of clinical development [ , ].



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a. Gene ontology analysis of differentially expressed genes of HAP-1 cells after 24 h treatment with 50 nM of NoA or DMSO vehicle control. b. Schematic of mitochondrial apoptosis regulation by BCL-2 family members. Chronic cellular stress <t>BH3-only</t> proteins upregulation antagonize pro-survival BCL-2 members and activate BAX/BAK, resulting in mitochondrial outer membrane permeabilization and apoptosis. c. Heatmap showing regulation of canonical ATF4 target genes extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. d. Heatmap showing regulation of canonical JUN target genes extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. e. Heatmap showing regulation of pro-apoptotic BH-3 proteins extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. f. Western blot analysis of HAP-1 WT cells treated with 50 nM NoA. Cells were harvested at 0, 3, 6, 12 and 24 h after treatment, and protein lysates were probed with the indicated antibodies. g. Nalm-6 WT and KO clones were treated with 12, 25 and 50 nM of NoA. Annexin V surface binding and Propidium Iodide uptake was measured after 72 h to assess viability of the cells. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and KO clones. * P < 0.05, ** P < 0.005 h. Western blot analysis of Nalm-6 and HCT-116 WT cells treated with 50 nM NoA. Cells were harvested at 0, 12, 24 and 36 h after NoA treatment and protein lysates probed with indicated antibodies. MCL-1 OMM refers to the full-length, anti-apoptotic isoform MCL-1.
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Image Search Results


a. Gene ontology analysis of differentially expressed genes of HAP-1 cells after 24 h treatment with 50 nM of NoA or DMSO vehicle control. b. Schematic of mitochondrial apoptosis regulation by BCL-2 family members. Chronic cellular stress BH3-only proteins upregulation antagonize pro-survival BCL-2 members and activate BAX/BAK, resulting in mitochondrial outer membrane permeabilization and apoptosis. c. Heatmap showing regulation of canonical ATF4 target genes extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. d. Heatmap showing regulation of canonical JUN target genes extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. e. Heatmap showing regulation of pro-apoptotic BH-3 proteins extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. f. Western blot analysis of HAP-1 WT cells treated with 50 nM NoA. Cells were harvested at 0, 3, 6, 12 and 24 h after treatment, and protein lysates were probed with the indicated antibodies. g. Nalm-6 WT and KO clones were treated with 12, 25 and 50 nM of NoA. Annexin V surface binding and Propidium Iodide uptake was measured after 72 h to assess viability of the cells. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and KO clones. * P < 0.05, ** P < 0.005 h. Western blot analysis of Nalm-6 and HCT-116 WT cells treated with 50 nM NoA. Cells were harvested at 0, 12, 24 and 36 h after NoA treatment and protein lysates probed with indicated antibodies. MCL-1 OMM refers to the full-length, anti-apoptotic isoform MCL-1.

Journal: bioRxiv

Article Title: Inhibition of V-ATPase function drives apoptosis via GCN1/GCN2 kinase signaling

doi: 10.64898/2026.03.27.714872

Figure Lengend Snippet: a. Gene ontology analysis of differentially expressed genes of HAP-1 cells after 24 h treatment with 50 nM of NoA or DMSO vehicle control. b. Schematic of mitochondrial apoptosis regulation by BCL-2 family members. Chronic cellular stress BH3-only proteins upregulation antagonize pro-survival BCL-2 members and activate BAX/BAK, resulting in mitochondrial outer membrane permeabilization and apoptosis. c. Heatmap showing regulation of canonical ATF4 target genes extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. d. Heatmap showing regulation of canonical JUN target genes extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. e. Heatmap showing regulation of pro-apoptotic BH-3 proteins extracted from the RNA-seq data. Values show row scaled vst-normalized expression of differentially expressed genes. Values of n=4 technical replicates are shown. f. Western blot analysis of HAP-1 WT cells treated with 50 nM NoA. Cells were harvested at 0, 3, 6, 12 and 24 h after treatment, and protein lysates were probed with the indicated antibodies. g. Nalm-6 WT and KO clones were treated with 12, 25 and 50 nM of NoA. Annexin V surface binding and Propidium Iodide uptake was measured after 72 h to assess viability of the cells. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and KO clones. * P < 0.05, ** P < 0.005 h. Western blot analysis of Nalm-6 and HCT-116 WT cells treated with 50 nM NoA. Cells were harvested at 0, 12, 24 and 36 h after NoA treatment and protein lysates probed with indicated antibodies. MCL-1 OMM refers to the full-length, anti-apoptotic isoform MCL-1.

Article Snippet: Loss of MCL-1 creates a vulnerability that renders cells dependent on co-expressed BCL-2 family proteins, enabling potent synergy with the BH3 mimetics ABT-737 or venetoclax.

Techniques: Control, Membrane, RNA Sequencing, Expressing, Western Blot, Clone Assay, Binding Assay

a. Bottom: Representative cell cycle profiles of HAP-1 WT and BB dKO cells after exposure to 12.5, 25 and 50 nM of NoA. Right: Ǫuantification of the SubG1 population represented as bar graphs, showing means and SD of N=3 biological replicates. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing SubG1 percentages of corresponding concentrations of WT with BBdKO cells at every time point. **** P < 0.0001 b. HAP-1 WT and HAP-1 BB dKO KO cells were treated with 12.5, 25 and 50 nM of BafA1. Annexin V surface binding and Propidium Iodide uptake was measured after 48 and 72 h to assess viability of the cells. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and BB dKO cells at every time point. **** P < 0.0001. c. WB analysis of HAP-1 WT, GCN1 KO, and GCN2 KO cells treated with NoA or BafA1 (25 or 50 nM) for 24 h. Cell lysates were probed for the indicated proteins. d. HAP-1 WT and GCN1 KO cells were treated with BafA1 (6.25, 12.5, 25, or 50 nM). HAP-1 WT cells were treated either with BafA1 alone or in combination with the GCN2 inhibitor GCN2iB (10 μM). Annexin V surface binding and propidium iodide (PI) uptake were measured after 48 and 72 h to assess cell viability. Bar plots represent mean ± SD of three biological replicates. Legend: AV−/PI−, live cells; AV+/PI−, early apoptosis; AV+/PI+ and AV−/PI+, late apoptosis. Statistical significance was determined by two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells at corresponding concentrations between WT and GCN1 KO cells or WT cells co-treated with GCN2iB at each time point. ** P < 0.01, *** P < 0.001, ** P < 0.0001. e. HCT-116 WT and Octa KO clones were treated with 12.5, 25 and 5 0nM of BafA1. Annexin V surface binding and Propidium Iodide uptake was measured after 24, 48 and 72 h to assess cell viability. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and Octa KO clones. * P < 0.015, ** P < 0.004, *** P < 0.001, **** P < 0.0001 f. HAP-1 WT cells were treated with indicated V-ATPase inhibitors (25 nM) or ABT-737 (1 μM) alone or in combination for 24 h. Viability was assessed by Annexin V surface binding and Propidium Iodide uptake. Viable fraction was defined as double negative cells and is depicted as mean ± SD of three biological replicates. g. Dot plot showing synergy scores for combinations of V-ATPase inhibitors with BH3 mimetics (ABT-737 and ABT-199). Synergy scores were calculated using the SynergyFinder web tool based on concentration matrices of two biological replicates. Cell viability was defined as the fraction of Annexin V−/PI− (double-negative) cells, representing live cells. h. Proposed mechanism for V-ATPase inhibition induced cell death

Journal: bioRxiv

Article Title: Inhibition of V-ATPase function drives apoptosis via GCN1/GCN2 kinase signaling

doi: 10.64898/2026.03.27.714872

Figure Lengend Snippet: a. Bottom: Representative cell cycle profiles of HAP-1 WT and BB dKO cells after exposure to 12.5, 25 and 50 nM of NoA. Right: Ǫuantification of the SubG1 population represented as bar graphs, showing means and SD of N=3 biological replicates. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing SubG1 percentages of corresponding concentrations of WT with BBdKO cells at every time point. **** P < 0.0001 b. HAP-1 WT and HAP-1 BB dKO KO cells were treated with 12.5, 25 and 50 nM of BafA1. Annexin V surface binding and Propidium Iodide uptake was measured after 48 and 72 h to assess viability of the cells. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and BB dKO cells at every time point. **** P < 0.0001. c. WB analysis of HAP-1 WT, GCN1 KO, and GCN2 KO cells treated with NoA or BafA1 (25 or 50 nM) for 24 h. Cell lysates were probed for the indicated proteins. d. HAP-1 WT and GCN1 KO cells were treated with BafA1 (6.25, 12.5, 25, or 50 nM). HAP-1 WT cells were treated either with BafA1 alone or in combination with the GCN2 inhibitor GCN2iB (10 μM). Annexin V surface binding and propidium iodide (PI) uptake were measured after 48 and 72 h to assess cell viability. Bar plots represent mean ± SD of three biological replicates. Legend: AV−/PI−, live cells; AV+/PI−, early apoptosis; AV+/PI+ and AV−/PI+, late apoptosis. Statistical significance was determined by two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells at corresponding concentrations between WT and GCN1 KO cells or WT cells co-treated with GCN2iB at each time point. ** P < 0.01, *** P < 0.001, ** P < 0.0001. e. HCT-116 WT and Octa KO clones were treated with 12.5, 25 and 5 0nM of BafA1. Annexin V surface binding and Propidium Iodide uptake was measured after 24, 48 and 72 h to assess cell viability. Bar plots show mean ± SD of three biological replicates. Legend: AV−/PI− = live cells, AV+/PI− = early apoptosis, AV+/PI+ and AV−/PI+ = late apoptosis. Statistical significance was determined using a two-way ANOVA with Bonferroni correction for multiple comparisons, comparing percentages of live cells of corresponding concentrations between WT and Octa KO clones. * P < 0.015, ** P < 0.004, *** P < 0.001, **** P < 0.0001 f. HAP-1 WT cells were treated with indicated V-ATPase inhibitors (25 nM) or ABT-737 (1 μM) alone or in combination for 24 h. Viability was assessed by Annexin V surface binding and Propidium Iodide uptake. Viable fraction was defined as double negative cells and is depicted as mean ± SD of three biological replicates. g. Dot plot showing synergy scores for combinations of V-ATPase inhibitors with BH3 mimetics (ABT-737 and ABT-199). Synergy scores were calculated using the SynergyFinder web tool based on concentration matrices of two biological replicates. Cell viability was defined as the fraction of Annexin V−/PI− (double-negative) cells, representing live cells. h. Proposed mechanism for V-ATPase inhibition induced cell death

Article Snippet: Loss of MCL-1 creates a vulnerability that renders cells dependent on co-expressed BCL-2 family proteins, enabling potent synergy with the BH3 mimetics ABT-737 or venetoclax.

Techniques: Binding Assay, Clone Assay, Concentration Assay, Inhibition

a , Agarose gel electrophoresis after PCR amplification of the CAD genomic locus in wild-type and CAD KO HeLa cells. * indicates expected length of wild-type locus, ** indicates expected length of locus after CRISPR/Cas9-mediated partial deletion. b , Agarose gel electrophoresis of fragmented DNA isolated from wild-type and CAD KO cells in the presence and absence of romidepsin and BH3 mimetics. c , Imaging of fixed wild-type and CAD KO cells, stained for cleaved PARP and TUNEL signal. DNA was stained with SPY650. Scale bar 5 µm. d , Quantification of TUNEL signal normalised to chromatin density ( d ) and chromatin density ( e ) in fixed live and apoptotic wild-type and CAD KO cells, in the presence and absence of romidepsin. n =76 for live wild-type, n =103 for apoptotic wild-type, n =103 for apoptotic CAD KO (control); n =63 for live wild-type, n =77 for apoptotic wild-type, n =103 for apoptotic CAD KO (romidepsin). Bars indicate mean; significance was tested by a two-tailed Mann-Whitney test (apoptotic wild-type vs live wild-type, P =<0.0001 (TUNEL), P =<0.0001 (chromatin); apoptotic CAD KO vs apoptotic wild-type, P =<0.0001 (TUNEL), romidepsin-treated apoptotic wild-type vs control apoptotic wild-type, P =<0.0001 (chromatin)).

Journal: bioRxiv

Article Title: Electrostatic control of chromatin compaction safeguards against apoptotic DNA release

doi: 10.64898/2026.02.23.707452

Figure Lengend Snippet: a , Agarose gel electrophoresis after PCR amplification of the CAD genomic locus in wild-type and CAD KO HeLa cells. * indicates expected length of wild-type locus, ** indicates expected length of locus after CRISPR/Cas9-mediated partial deletion. b , Agarose gel electrophoresis of fragmented DNA isolated from wild-type and CAD KO cells in the presence and absence of romidepsin and BH3 mimetics. c , Imaging of fixed wild-type and CAD KO cells, stained for cleaved PARP and TUNEL signal. DNA was stained with SPY650. Scale bar 5 µm. d , Quantification of TUNEL signal normalised to chromatin density ( d ) and chromatin density ( e ) in fixed live and apoptotic wild-type and CAD KO cells, in the presence and absence of romidepsin. n =76 for live wild-type, n =103 for apoptotic wild-type, n =103 for apoptotic CAD KO (control); n =63 for live wild-type, n =77 for apoptotic wild-type, n =103 for apoptotic CAD KO (romidepsin). Bars indicate mean; significance was tested by a two-tailed Mann-Whitney test (apoptotic wild-type vs live wild-type, P =<0.0001 (TUNEL), P =<0.0001 (chromatin); apoptotic CAD KO vs apoptotic wild-type, P =<0.0001 (TUNEL), romidepsin-treated apoptotic wild-type vs control apoptotic wild-type, P =<0.0001 (chromatin)).

Article Snippet: We induced apoptosis using Bcl-2 Homology domain 3 (BH3) mimetics , confirming cell death by poly-ADP ribose polymerase (PARP) cleavage, and we synchronised parallel cultures to mitosis, verifying mitotic entry via anti-phospho-Ser/Thr-Pro antibody (MPM-2) staining.

Techniques: Agarose Gel Electrophoresis, Amplification, CRISPR, Isolation, Imaging, Staining, TUNEL Assay, Control, Two Tailed Test, MANN-WHITNEY

a , Flow cytometry plots of control and BH3 mimetic-treated cells. Apoptotic cells and ApoEVs were detected by Annexin V-488 staining, and ApoEVs were distinguished from cells based on size. b , Quantification of apoptotic entry efficiency, the percentage of total cells in apoptosis n =3 for all conditions. Bars indicate mean. c , Quantification of apoptotic ApoEV production, the number of ApoEVs per apoptotic cell n =3 for all conditions. Bars indicate mean. d , Flow cytometry plots of DNA and cytosol content in ApoEVs from apoptotic wild-type and CAD KO cells, in the presence and absence of romidepsin. DNA was stained with SPY650 and cytosol with CellTrace Yellow. Solid line represents threshold for positive DNA staining, dotted line represents threshold for positive cytosolic staining. Thresholds were defined by unstained controls. DNA percentages displayed as mean values across three biological replicates. e, f , Quantification of ApoEV DNA ( e ) and cytosol ( f ) content, as a percentage of all ApoEVs. n =3 for all conditions. Bars indicate mean; significance was tested by a parametric paired t-test (DNA content in romidepsin-treated wild-type vs control wild-type, P =0.0031). g , Imaging of DNA and cytosol within ApoEVs. ApoEVs were stained with Annexin V-488, DNA with SPY650 and cytosol with CellTrace Yellow. Contours in the lower panels were drawn from the outer contour of Annexin V staining. Scale bar 5 µm. h, i , Quantification of imaged ApoEV DNA ( h ) and cytosol ( i ) content, as a percentage of all ApoEVs. n =3 for all conditions. Bars indicate mean; significance was tested by a parametric paired t-test (DNA content in romidepsin-treated wild-type vs control wild-type, P =0.0039).

Journal: bioRxiv

Article Title: Electrostatic control of chromatin compaction safeguards against apoptotic DNA release

doi: 10.64898/2026.02.23.707452

Figure Lengend Snippet: a , Flow cytometry plots of control and BH3 mimetic-treated cells. Apoptotic cells and ApoEVs were detected by Annexin V-488 staining, and ApoEVs were distinguished from cells based on size. b , Quantification of apoptotic entry efficiency, the percentage of total cells in apoptosis n =3 for all conditions. Bars indicate mean. c , Quantification of apoptotic ApoEV production, the number of ApoEVs per apoptotic cell n =3 for all conditions. Bars indicate mean. d , Flow cytometry plots of DNA and cytosol content in ApoEVs from apoptotic wild-type and CAD KO cells, in the presence and absence of romidepsin. DNA was stained with SPY650 and cytosol with CellTrace Yellow. Solid line represents threshold for positive DNA staining, dotted line represents threshold for positive cytosolic staining. Thresholds were defined by unstained controls. DNA percentages displayed as mean values across three biological replicates. e, f , Quantification of ApoEV DNA ( e ) and cytosol ( f ) content, as a percentage of all ApoEVs. n =3 for all conditions. Bars indicate mean; significance was tested by a parametric paired t-test (DNA content in romidepsin-treated wild-type vs control wild-type, P =0.0031). g , Imaging of DNA and cytosol within ApoEVs. ApoEVs were stained with Annexin V-488, DNA with SPY650 and cytosol with CellTrace Yellow. Contours in the lower panels were drawn from the outer contour of Annexin V staining. Scale bar 5 µm. h, i , Quantification of imaged ApoEV DNA ( h ) and cytosol ( i ) content, as a percentage of all ApoEVs. n =3 for all conditions. Bars indicate mean; significance was tested by a parametric paired t-test (DNA content in romidepsin-treated wild-type vs control wild-type, P =0.0039).

Article Snippet: We induced apoptosis using Bcl-2 Homology domain 3 (BH3) mimetics , confirming cell death by poly-ADP ribose polymerase (PARP) cleavage, and we synchronised parallel cultures to mitosis, verifying mitotic entry via anti-phospho-Ser/Thr-Pro antibody (MPM-2) staining.

Techniques: Flow Cytometry, Control, Staining, Imaging