ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
AMG-176, an Mcl-1 Antagonist, Shows Preclinical Efficacy in Chronic Lymphocytic Leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
The trial behind it
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
38 citing papers in PubMed, 62 citations in OpenAlex.
- Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.Blood cancer journal · 2026Trial
- The use of venetoclax in the treatment of acute lymphoblastic leukemia-a systematic review.Therapeutic advances in medical oncology · 2026Review
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- Pitavastatin is a novel Mcl-1 inhibitor that overcomes paclitaxel resistance in triple-negative breast cancer.Experimental hematology & oncology · 2025Article
- Re-appraising assays on permeabilized blood cancer cells testing venetoclax or other BH3 mimetic agents selectively targeting pro-survival BCL2 proteins.Cell death and differentiation · 2025Article
- Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed/refractory multiple myeloma.Haematologica · 2025Article
- Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.MedComm · 2024Review
- Unlocking the Therapeutic Potential of BCL-2 Associated Protein Family: Exploring BCL-2 Inhibitors in Cancer Therapy.Biomolecules & therapeutics · 2024Review
- Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.Molecular cell · 2024Article
- KS18, a Mcl-1 inhibitor, improves the effectiveness of bortezomib and overcomes resistance in refractory multiple myeloma by triggering intrinsic apoptosis.Frontiers in pharmacology · 2024Article
- MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes.Frontiers in immunology · 2024Review
- Decoding the mechanism behind MCL-1 inhibitors: A pathway to understanding MCL-1 protein stability.Oncotarget · 2023Article
- Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers.International journal of molecular sciences · 2023Review
- AMG176, an MCL-1 inhibitor, is active in pre-clinical models of aggressive B-cell lymphomas.Leukemia & lymphoma · 2023Article
- Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- Article
- Targeting Mcl-1 by AMG-176 During Ibrutinib and Venetoclax Therapy in Chronic Lymphocytic Leukemia.Frontiers in oncology · 2022Article
- Indoleamine 2, 3-Dioxygenase 1 Mediates Survival Signals in Chronic Lymphocytic LeukemiaFrontiers in immunology · 2022Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 3 countries.
Funding
Abstract
purposeSurvival of CLL cells due to the presence of Bcl-2 and Mcl-1 has been established. Direct inhibition of Bcl-2 by venetoclax and indirect targeting of Mcl-1 with transcription inhibitors have been successful approaches for CLL. AMG-176 is a selective and direct antagonist of Mcl-1, which has shown efficacy in several hematologic malignancies; however, its effect on CLL is elusive. We evaluated biological and molecular effects of AMG-176 in primary CLL cells. EXPERIMENTAL
designUsing samples from patients (
resultsAMG-176 incubations resulted in time- and dose-dependent CLL cell death. At 100 and 300 nmol/L, there was 30% and 45% cell death at 24 hours. These concentrations did not result in significant cell death in normal hematopoietic cells. Presence of stroma did not affect AMG-176-induced CLL cell death. IGHV unmutated status, high β2M and Mcl-1 protein levels resulted in slightly lower cell death. Mcl-1, but not Bcl-2 protein levels, in CLL cells increased with AMG-176. Low concentrations of venetoclax (1-30 nmol/L) were additive or synergistic with AMG-176.
conclusionsAMG-176 is active in inducing CLL cell death while sparing normal blood cells. Combination with low-dose venetoclax was additive or synergistic.
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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.