ArticleAging cell2020
Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 264 citations in OpenAlex.
- Senogenic-senolytic treatment strategies enhance tumor control and can improve survival in murine cancer models: a systematic review.BMC cancer · 2026Pooled it
- Therapy-Induced Senescence in Cancer Treatment Resistance: Mechanisms, Evidence, and Translational Opportunities.Cancers · 2026Review
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- The vicious cycle of SASP and inflammaging promotes aging and age-related diseases.Communications biology · 2026Review
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Natural products targeting cytokine-regulated SASP inflammation networks in Ovarian cancer: Implications on immune escape and molecular resistance.Inflammopharmacology · 2026Review
- Cellular senescence and inflammageing: from mechanisms to senotherapeutic interventions.Biogerontology · 2026Review
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- An SSK1-loaded decellularized annulus fibrosus matrix-based PD hydrogel alleviates intervertebral disc degeneration through modulation of NF-κB signaling and ferroptosis.Journal of orthopaedic translation · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Urinary detection of therapy-induced senescence and fibrosis using an injectable albumin-based nanoprobe.Nature aging · 2026Article
- Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability.Nature cell biology · 2026Article
- Review
- Engineered bacteria reprogram tumor microenvironmentActa pharmaceutica Sinica. B · 2026Article
- Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming.npj aging · 2026Review
- The Senolytic Drug Navitoclax Protects the Brain After Experimental Ischemic Stroke.Pharmaceuticals (Basel, Switzerland) · 2026Article
- p21-Positive Senescent Stromal Cells Promote Prostate Cancer Immune Suppression and Progression That Can Be Reversed by Senolytic Therapy.Cancer discovery · 2026Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence-associated lysosomal β-galactosidase (SA-β-gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose-encapsulated nanoparticles within these cells. Here, we show that galacto-conjugation of the BCL-2 family inhibitor Navitoclax results in a potent senolytic prodrug (Nav-Gal), that can be preferentially activated by SA-β-gal activity in a wide range of cell types. Nav-Gal selectively induces senescent cell apoptosis and has a higher senolytic index than Navitoclax (through reduced activation in nonsenescent cells). Nav-Gal enhances the cytotoxicity of standard senescence-inducing chemotherapy (cisplatin) in human A549 lung cancer cells. Concomitant treatment with cisplatin and Nav-Gal in vivo results in the eradication of senescent lung cancer cells and significantly reduces tumour growth. Importantly, galacto-conjugation reduces Navitoclax-induced platelet apoptosis in human and murine blood samples treated ex vivo, and thrombocytopenia at therapeutically effective concentrations in murine lung cancer models. Taken together, we provide a potentially versatile strategy for generating effective senolytic prodrugs with reduced toxicities.
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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.