Nature Communications (Apr 2020)
Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity
- Yonghan He,
- Xuan Zhang,
- Jianhui Chang,
- Ha-Neui Kim,
- Peiyi Zhang,
- Yingying Wang,
- Sajid Khan,
- Xingui Liu,
- Xin Zhang,
- Dongwen Lv,
- Lin Song,
- Wen Li,
- Dinesh Thummuri,
- Yaxia Yuan,
- Janet S. Wiegand,
- Yuma T. Ortiz,
- Vivekananda Budamagunta,
- Jennifer H. Elisseeff,
- Judith Campisi,
- Maria Almeida,
- Guangrong Zheng,
- Daohong Zhou
Affiliations
- Yonghan He
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Xuan Zhang
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Jianhui Chang
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences
- Ha-Neui Kim
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences
- Peiyi Zhang
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Yingying Wang
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences
- Sajid Khan
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Xingui Liu
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Xin Zhang
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Dongwen Lv
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Lin Song
- Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences
- Wen Li
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Dinesh Thummuri
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Yaxia Yuan
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Janet S. Wiegand
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Yuma T. Ortiz
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Vivekananda Budamagunta
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Jennifer H. Elisseeff
- Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine
- Judith Campisi
- Buck Institute for Research on Aging
- Maria Almeida
- Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences
- Guangrong Zheng
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Daohong Zhou
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- DOI
- https://doi.org/10.1038/s41467-020-15838-0
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 14
Abstract
Senolytics have the potential to extend healthspan by selectively killing senescent cells (SCs), but senolytics that target Bcl-xl may cause platelet toxicity. Here, the authors generated a Bcl-xl proteolysis-targeting chimera (PROTAC) senolytic, which effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia.
