ArticleNature communications2020
Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
What it found
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Who cites it
158 citing papers in PubMed, 249 citations in OpenAlex.
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Therapy-Induced Senescence in Cancer Treatment Resistance: Mechanisms, Evidence, and Translational Opportunities.Cancers · 2026Review
- Transmembrane Protein PTCHD4 Is a Novel Regulator of Cellular Senescence and Age-Related Pathologies.Aging cell · 2026Article
- A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions.Aging cell · 2026Review
- Pathological Mechanism-Inspired Biomimetic Nano-Senotherapy for Reversing Experimental Atherosclerosis in ApoEAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Primate-Specific lncRNA LINC01021 Contributes to Cellular and Organismal Aging via DAZAP1-Dependent Destabilization of RBMX.Aging cell · 2026Article
- POLY-Senolytic nanoplatform for tumor-specific eradication of senescent tumor cells and mitigation of radiotherapy-induced immune resistance of cancer.Nature communications · 2026Article
- Cellular senescence as a therapeutic target for aging intervention.Biomedical journal · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Proteolysis-targeting chimera (PROTAC) in cancer: design principles and applications on "undruggable" targets.Biomarker research · 2026Review
- From undruggable to degradable: A deep learning-enabled framework for precision orthopaedic protein degradation.Journal of orthopaedic translation · 2026Review
- Clearance of Senescent Cells by BCLAging cell · 2026Article
- Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming.npj aging · 2026Review
- p21-Positive Senescent Stromal Cells Promote Prostate Cancer Immune Suppression and Progression That Can Be Reversed by Senolytic Therapy.Cancer discovery · 2026Article
- The Role of Cellular Senescence in Oral Health and Disease.International journal of molecular sciences · 2026Review
- Senotoxins target senescence via lipid binding specificity, ion imbalance and lipidome remodeling.Nature aging · 2026Article
- Revolutionizing cancer treatment with senotherapeutics: a current perspective.Cancer chemotherapy and pharmacology · 2026Review
- Targeting BCL-XL for degradation synergizes with gemcitabine against cholangiocarcinoma.BMC medicine · 2026Article
- Review
98 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Small molecules that selectively kill senescent cells (SCs), termed senolytics, have the potential to prevent and treat various age-related diseases and extend healthspan. The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity. Here, we report the use of proteolysis-targeting chimera (PROTAC) technology to reduce the platelet toxicity of navitoclax (also known as ABT263), a Bcl-2 and Bcl-xl dual inhibitor, by converting it into PZ15227 (PZ), a Bcl-xl PROTAC, which targets Bcl-xl to the cereblon (CRBN) E3 ligase for degradation. Compared to ABT263, PZ is less toxic to platelets, but equally or slightly more potent against SCs because CRBN is poorly expressed in platelets. PZ effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia. With further improvement, Bcl-xl PROTACs have the potential to become safer and more potent senolytic agents than Bcl-xl inhibitors.
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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.