ArticleBlood2024
Sonrotoclax overcomes BCL2 G101V mutation-induced venetoclax resistance in preclinical models of hematologic malignancy.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Phase I/II Study of Sonrotoclax (BGB-11417) Monotherapy in Patients With Mantle Cell Lymphoma Previously Treated With Anti-CD20 Therapy and a Bruton Tyrosine Kinase Inhibitor.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer.Signal transduction and targeted therapy · 2026Trial
- Molecular Pharmacological Characterization of Dicentrine Isolated fromInternational journal of molecular sciences · 2026Article
- Metabolism and Immunity-Adapted Radiotherapy (M.I.A.R): A Conceptual Framework for Overcoming the Therapeutic Plateau in Clinical Radiotherapy.Current oncology (Toronto, Ont.) · 2026Review
- Apigenin as a Multitarget Anticancer Agent: Coordinated Inhibition of EGFR/MAPK and PI3K/Akt Signaling in Hematologic Malignancies.International journal of molecular sciences · 2026Article
- Breaking the bonds: targeting protein dimerization for prostate cancer therapy.Endocrinology · 2026Review
- Bcl-xL blockade targets neutrophils and synergizes with chemotherapy in lung squamous cell carcinoma.EMBO molecular medicine · 2026Article
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- Have Fixed-Duration (FD) Regimens Delivered on Their Promise in Chronic Lymphocytic Leukemia and What Is the Future of FD Regimens? A Narrative Review.Advances in therapy · 2026Review
- When Targeted Therapy Falls Short: Unraveling Resistance Mechanisms in Chronic Lymphocytic Leukemia.Current hematologic malignancy reports · 2026Review
- Navigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics.Chemical science · 2026Review
- Phase Ib study of enzalutamide with venetoclax in patients with metastatic castration-resistant prostate cancer.Cancer chemotherapy and pharmacology · 2025Article
- The Development of Novel Therapies for Chronic Lymphocytic Leukaemia in the Era of Targeted Drugs.Journal of clinical medicine · 2025Review
- Inhibition of FOXM1 Synergizes with BH3 Mimetics Venetoclax and Sonrotoclax in Killing Multiple Myeloma Cells through Repressing MYC Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.Leukemia · 2025Review
- Relapsed childhood T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.Haematologica · 2025Review
- Biotransformation and disposition of CCancer chemotherapy and pharmacology · 2025Article
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- JCMM Annual Review on Advances in Biotechnology for the Treatment of Haematological Malignancies: A Review of the Latest In-Patient Developments 2024-2025.Journal of cellular and molecular medicine · 2025Review
- Resistance mechanisms and approach to chronic lymphocytic leukemia after BTK inhibitor therapy.Leukemia & lymphoma · 2025Review
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Authors and funding
35 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
abstractVenetoclax, the first-generation inhibitor of the apoptosis regulator B-cell lymphoma 2 (BCL2), disrupts the interaction between BCL2 and proapoptotic proteins, promoting the apoptosis in malignant cells. Venetoclax is the mainstay of therapy for relapsed chronic lymphocytic leukemia and is under investigation in multiple clinical trials for the treatment of various cancers. Although venetoclax treatment can result in high rates of durable remission, relapse has been widely observed, indicating the emergence of drug resistance. The G101V mutation in BCL2 is frequently observed in patients who relapsed treated with venetoclax and sufficient to confer resistance to venetoclax by interfering with compound binding. Therefore, the development of next-generation BCL2 inhibitors to overcome drug resistance is urgently needed. In this study, we discovered that sonrotoclax, a potent and selective BCL2 inhibitor, demonstrates stronger cytotoxic activity in various hematologic cancer cells and more profound tumor growth inhibition in multiple hematologic tumor models than venetoclax. Notably, sonrotoclax effectively inhibits venetoclax-resistant BCL2 variants, such as G101V. The crystal structures of wild-type BCL2/BCL2 G101V in complex with sonrotoclax revealed that sonrotoclax adopts a novel binding mode within the P2 pocket of BCL2 and could explain why sonrotoclax maintains stronger potency than venetoclax against the G101V mutant. In summary, sonrotoclax emerges as a potential second-generation BCL2 inhibitor for the treatment of hematologic malignancies with the potential to overcome BCL2 mutation-induced venetoclax resistance. Sonrotoclax is currently under investigation in multiple clinical trials.
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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.