Nature Communications (Nov 2021)
Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity,
- Dongwen Lv,
- Pratik Pal,
- Xingui Liu,
- Yannan Jia,
- Dinesh Thummuri,
- Peiyi Zhang,
- Wanyi Hu,
- Jing Pei,
- Qi Zhang,
- Shuo Zhou,
- Sajid Khan,
- Xuan Zhang,
- Nan Hua,
- Qingping Yang,
- Sebastian Arango,
- Weizhou Zhang,
- Digant Nayak,
- Shaun K. Olsen,
- Susan T. Weintraub,
- Robert Hromas,
- Marina Konopleva,
- Yaxia Yuan,
- Guangrong Zheng,
- Daohong Zhou
Affiliations
- Dongwen Lv
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Pratik Pal
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Xingui Liu
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Yannan Jia
- Department of Leukemia, University of Texas M.D. Anderson Cancer Center
- Dinesh Thummuri
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Peiyi Zhang
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Wanyi Hu
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Jing Pei
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Qi Zhang
- Department of Leukemia, University of Texas M.D. Anderson Cancer Center
- Shuo Zhou
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Sajid Khan
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Xuan Zhang
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida
- Nan Hua
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Qingping Yang
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Sebastian Arango
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- Weizhou Zhang
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida
- Digant Nayak
- Department of Biochemistry & Structure Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio
- Shaun K. Olsen
- Department of Biochemistry & Structure Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio
- Susan T. Weintraub
- Department of Biochemistry & Structure Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio
- Robert Hromas
- Mays Cancer Center, the Long School of Medicine, University of Texas Health Science Center at San Antonio
- Marina Konopleva
- Department of Leukemia, University of Texas M.D. Anderson Cancer Center
- Yaxia Yuan
- Department of Pharmacodynamics, College of Pharmacy, University of Florida
- 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/s41467-021-27210-x
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 14
Abstract
Simultaneous targeting of BCL-xL and BCL-2 is an attractive approach for cancer treatment. Based on information gained by computational structure modelling, the authors develop a PROTAC that induces degradation of both BCL-xL and BCL-2 and effectively targets BCL-xL/2-dependent leukaemia cells.
