Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry
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
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Nature Portfolio
2020
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| Acceso en línea: | https://doaj.org/article/4979b2c9fe654e15a019e2b5da2998c8 |
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oai:doaj.org-article:4979b2c9fe654e15a019e2b5da2998c82021-12-02T19:02:36ZEnhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry10.1038/s41467-020-17997-62041-1723https://doaj.org/article/4979b2c9fe654e15a019e2b5da2998c82020-08-01T00:00:00Zhttps://doi.org/10.1038/s41467-020-17997-6https://doaj.org/toc/2041-1723PROTACs 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 kinaseWen-Hao GuoXiaoli QiXin YuYang LiuChan-I ChungFang BaiXingcheng LinDong LuLingfei WangJianwei ChenLynn Hsiao SuKrystle J. NomieFeng LiMeng C. WangXiaokun ShuJosé N. OnuchicJennifer A. WoyachMichael L. WangJin WangNature PortfolioarticleScienceQENNature Communications, Vol 11, Iss 1, Pp 1-16 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Science Q |
| spellingShingle |
Science Q 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 Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry |
| description |
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 |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Wen-Hao Guo |
| title |
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry |
| title_short |
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry |
| title_full |
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry |
| title_fullStr |
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry |
| title_full_unstemmed |
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry |
| title_sort |
enhancing intracellular accumulation and target engagement of protacs with reversible covalent chemistry |
| publisher |
Nature Portfolio |
| publishDate |
2020 |
| url |
https://doaj.org/article/4979b2c9fe654e15a019e2b5da2998c8 |
| work_keys_str_mv |
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| _version_ |
1718377207194189824 |