A patent review of SCF E3 ligases inhibitors for cancerï¼Structural design, pharmacological activities and structure-activity relationship.

Zeng, Jing; Chen, Zheng; He, Yuxin; Jiang, Zhongliang; Zhang, Yi; Dong, Qin; Chen, Liping; Deng, Sichun; He, Ziyou; Li, Ling; Li, Jinqi; Shi, Jianyou

A patent review of SCF E3 ligases inhibitors for cancerï¼Structural design, pharmacological activities and structure-activity relationship.

Zeng, Jing; Chen, Zheng; He, Yuxin; Jiang, Zhongliang; Zhang, Yi; Dong, Qin; Chen, Liping; Deng, Sichun; He, Ziyou; Li, Ling; Li, Jinqi; Shi, Jianyou.

Afiliação

Zeng J; School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China.
Chen Z; School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
He Y; School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China.
Jiang Z; Hematology Department, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Zhang Y; School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China.
Dong Q; School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China.
Chen L; School of Comprehensive Health Management, Xihua University, Chengdu, 610039, China.
Deng S; School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China.
He Z; School of Economics and Management, The University of Hong Kong, Hong Kong, 999077, China.
Li L; School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China; Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, Sichuan, 611137, China. Electronic address: 0120030074@mail.xhu.edu.cn.
Li J; Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China. Electronic address: lijinqi2002@1
Shi J; Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China. Electronic address: shijianyoude@

Eur J Med Chem ; 278: 116821, 2024 Nov 15.

Article em En | MEDLINE | ID: mdl-39232359

ABSTRACT

ABSTRACT

Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, ß-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, ß-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target for the development of anti-cancer drugs. Over the past few decades, a variety of anti-tumor inhibitors targeting the SCF E3 ligase complex have been attempted. However, since almost none of the SCF E3 ligase inhibitors passed clinical trials, the design and synthesis of the new inhibitors are needed. Here, we will introduce the structure and function of Skp2, ß-TrCP, and FBXW7, their connections with cancer development, the relevant in vitro and in vivo activities, selectivity, structure-activity relationships, and the therapeutic or preventive application of small molecule inhibitors targeting these three F-box proteins reported in the patent (2010-present). This information will help develop drugs targeting the SCF E3 ubiquitin ligase, providing new strategies for future cancer treatments.

Assuntos

Antineoplásicos; Desenho de Fármacos; Neoplasias; Humanos; Relação Estrutura-Atividade; Antineoplásicos/farmacologia; Antineoplásicos/química; Antineoplásicos/síntese química; Neoplasias/tratamento farmacológico; Neoplasias/patologia; Patentes como Assunto; Animais; Proteínas Ligases SKP Culina F-Box/metabolismo; Proteínas Ligases SKP Culina F-Box/antagonistas & inibidores; Estrutura Molecular; Inibidores Enzimáticos/farmacologia; Inibidores Enzimáticos/química; Inibidores Enzimáticos/síntese química; Ubiquitina-Proteína Ligases/antagonistas & inibidores; Ubiquitina-Proteína Ligases/metabolismo; Proteínas Quinases Associadas a Fase S/antagonistas & inibidores; Proteínas Quinases Associadas a Fase S/metabolismo; Proteína 7 com Repetições F-Box-WD/metabolismo

Palavras-chave

Cancer; FBXW7; Inhibitors; SCF E3 ligases; Skp2; Structure-activity relationship; ß-TrCP

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Desenho de Fármacos / Neoplasias / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: França

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