Nature Communications (Aug 2020)
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry
- Wen-Hao Guo,
- Xiaoli Qi,
- Xin Yu,
- Yang Liu,
- Chan-I Chung,
- Fang Bai,
- Xingcheng Lin,
- Dong Lu,
- Lingfei Wang,
- Jianwei Chen,
- Lynn Hsiao Su,
- Krystle J. Nomie,
- Feng Li,
- Meng C. Wang,
- Xiaokun Shu,
- José N. Onuchic,
- Jennifer A. Woyach,
- Michael L. Wang,
- Jin Wang
Affiliations
- Wen-Hao Guo
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Xiaoli Qi
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Xin Yu
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Yang Liu
- Division of Cancer Medicine, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center
- Chan-I Chung
- Department of Pharmaceutical Chemistry, University of California−San Francisco
- Fang Bai
- Center for Theoretical Biological Physics, Rice University
- Xingcheng Lin
- Department of Chemistry, Massachusetts Institute of Technology
- Dong Lu
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Lingfei Wang
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Jianwei Chen
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Lynn Hsiao Su
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- Krystle J. Nomie
- Division of Cancer Medicine, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center
- Feng Li
- Department of Pathology and Immunology, Baylor College of Medicine
- Meng C. Wang
- Department of Molecular and Human Genetics, Baylor College of Medicine
- Xiaokun Shu
- Department of Pharmaceutical Chemistry, University of California−San Francisco
- José N. Onuchic
- Center for Theoretical Biological Physics, Rice University
- Jennifer A. Woyach
- Division of Hematology, Department of Internal Medicine, The Ohio State University
- Michael L. Wang
- Division of Cancer Medicine, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center
- Jin Wang
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine
- DOI
- https://doi.org/10.1038/s41467-020-17997-6
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 16
Abstract
PROTACs have emerged as promising therapeutic agents but their cellular uptake is often inefficient. Here, the authors show that reversible covalent warhead chemistry improves PROTAC intracellular accumulation and target engagement, and develop a dual inhibitor/degrader of Bruton’s tyrosine kinase
