ReviewMolecular cancer therapeutics2016
BCL2 Inhibitors as Anticancer Drugs: A Plethora of Misleading BH3 Mimetics.
Review in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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
63 citing papers in PubMed, 124 citations in OpenAlex.
- A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors.Investigational new drugs · 2020Trial
- Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1.Cell death & disease · 2026Article
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-XBritish journal of haematology · 2026Article
- Cancer Cell Cytotoxicity of Marinopyrroles, Pyrrolomycins, and Their Derivatives.Marine drugs · 2025Review
- Transformation to Neuroendocrine Phenotype in Non-Small-Cell Lung Carcinoma: A Literature Review.International journal of molecular sciences · 2025Review
- Transformation of lung adenocarcinoma to small cell lung cancer following osimertinib treatment: a case report and literature review.Anti-cancer drugs · 2025Review
- Novel 4-alkoxy Meriolin Congeners Potently Induce Apoptosis in Leukemia and Lymphoma Cells.Molecules (Basel, Switzerland) · 2024Article
- MDM2 drives resistance to Osimertinib by contextually disrupting FBW7-mediated destruction of MCL-1 protein in EGFR mutant NSCLC.Journal of experimental & clinical cancer research : CR · 2024Article
- A Phase 1 First-in-Human Study of the MCL-1 Inhibitor AZD5991 in Patients with Relapsed/Refractory Hematologic Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs).Cell death discovery · 2024Article
- The Role of Bcl-2 Family Proteins and Sorafenib Resistance in Hepatocellular Carcinoma.International journal of cell biology · 2024Review
- In silico design and cell-based evaluation of two dual anti breast cancer compounds targeting Bcl-2 and GPER.Scientific reports · 2023Article
- Genetic mutations affecting mitochondrial function in cancer drug resistance.Genes & genomics · 2023Review
- AMPK regulates homeostasis of invasion and viability in trophoblasts by redirecting glucose metabolism: Implications for pre-eclampsia.Cell proliferation · 2023Article
- Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics.International journal of biological sciences · 2023Review
- Harnessing the cyclization strategy for new drug discovery.Acta pharmaceutica Sinica. B · 2022Review
- Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells.Science advances · 2022Article
- Fragment-Based Drug Discovery by NMR. Where Are the Successes and Where can It Be Improved?Frontiers in molecular biosciences · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Antiapoptotic BCL2 proteins play a major role in tumor cell survival. Hence, BCL2 inhibitors have been developed as direct inducers of apoptosis. ABT-199 (venetoclax) received breakthrough therapy designation from the FDA due to its apparent efficacy in CLL and AML. However, resistance to ABT-199 is mediated by other BCL2 proteins including BCLXL and MCL1. Considerable effort has been expended seeking novel "BH3 mimetics" that inhibit all of these BCL2 proteins. While many BH3 mimetics inhibit BCL2 proteins in vitro, they fail to directly inhibit them in intact cells. Many BH3 mimetics induce the unfolded protein response culminating in induction of the proapoptotic protein NOXA, which in turn inhibits MCL1. We propose simple experiments to validate BH3 mimetics in cells. A true BCL2 inhibitor will rapidly induce apoptosis in chronic lymphocytic leukemia cells ex vivo A BCLXL inhibitor will rapidly induce apoptosis in platelets. Finally, a BH3 mimetic targeting MCL1 will inhibit its degradation thereby inducing rapid MCL1 accumulation. Compounds that fail these tests should no longer be called BH3 mimetics. We now have a toolbox of selective inhibitors for most of the BCL2 proteins, and we hope these new tools will lead to effective treatment options for many cancers. Mol Cancer Ther; 15(9); 2011-7. ©2016 AACR.
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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.