Discovery of N-Benzylpiperidinol derivatives as USP7 inhibitors against Hematology.

Pan, Youlu; Chen, Haifeng; Fu, Jingfeng; Zhang, Jingyu; Wang, Peipei; Chen, Runmei; Geng, Shuangshuang; Che, Jinxin; Dong, Xiaowu; Zhou, Yubo; Huang, Wenhai

Pan, Youlu; Chen, Haifeng; Fu, Jingfeng; Zhang, Jingyu; Wang, Peipei; Chen, Runmei; Geng, Shuangshuang; Che, Jinxin; Dong, Xiaowu; Zhou, Yubo; Huang, Wenhai.

Afiliación

Pan Y; Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310058, China.
Chen H; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Fu J; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong 528400, China.
Zhang J; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People's Hospital, Cancer Ce
Wang P; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong 528400, China.
Chen R; Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310058, China.
Geng S; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Che J; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Dong X; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Zhou Y; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong 528400, China. Electronic address: ybzhou@simm.ac.cn.
Huang W; Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310058, China. Electronic address: hwh@hmc.edu.cn.

Bioorg Chem ; 153: 107807, 2024 Sep 12.

Article en En | MEDLINE | ID: mdl-39293304

ABSTRACT

ABSTRACT

USP7 has been recognized as a potential target for the treatment of hematologic malignancies by stabilizing multiple cancer-relevant proteins. Nevertheless, drug-like USP7 inhibitors are still lacking. Herein, compound J21 (USP7 IC50 41.35 ± 2.16 nM) was discovered based on the structure of L55 and its co-crystal complex with USP7. Additionally, J21 exhibited greater metabolic stability (T1/2 1.25 h, Cmax 394.1 ± 48.3 ng/mL, and AUC0-t 597.8 ± 44.8 ng/mLâh) compared to L55. These findings may further pave the way for the development of USP7 inhibitors for the treatment of hematologic malignancies.

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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