Strategies for designing proteolysis targeting chimaeras (PROTACs) DOI
Shipeng He, Guoqiang Dong,

Junfei Cheng

и другие.

Medicinal Research Reviews, Год журнала: 2022, Номер 42(3), С. 1280 - 1342

Опубликована: Янв. 10, 2022

Abstract Proteolysis targeting chimaeras (PROTACs) is a cutting edge and rapidly growing technique for new drug discovery development. Currently, the largest challenge in molecular design development of PROTACs efficient identification potent drug‐like degraders. This review aims to comprehensively summarize analyse state‐of‐the‐art methods strategies PROTACs. We provide detailed illustration general principles tactics designing PROTACs, highlight representative case studies, discuss advantages limitations these strategies. Particularly, structure‐based rational PROTAC emerging types (e.g., homo‐PROTACs, multitargeting photo‐control PROTAC‐based conjugates) will be focused on.

Язык: Английский

Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development DOI
Pan Tang, Jifa Zhang, Jie Liu

и другие.

Journal of Medicinal Chemistry, Год журнала: 2021, Номер 64(5), С. 2419 - 2435

Опубликована: Фев. 22, 2021

Bromodomain and extraterminal (BET) proteins bind acetylated lysine residues in histones nonhistone via tandem bromodomains regulate chromatin dynamics, cellular processes, disease procession. Thus targeting BET is a promising strategy for treating various diseases, especially malignant tumors chronic inflammation. Many pan-BET small-molecule inhibitors have been described, some of them are clinical evaluation. Nevertheless, the limited efficacy current also evident has inspired development new technologies to improve their outcomes minimize unwanted side effects. In this Review, we summarize latest protein characteristics biological functions BRD4 as an example proteins, analyze status preclinical resistance mechanisms, discuss recent advances BRD4-selective inhibitors, dual-target proteolysis chimera degraders, protein–protein interaction inhibitors.

Язык: Английский

Процитировано

111

Protein acylation: mechanisms, biological functions and therapeutic targets DOI Creative Commons
Shuang Shang, Jing Liu, Fang Hua

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 29, 2022

Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular and infectious diseases. With progress metabonomics proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing activities acyltransferases deacylases. Reciprocally, acylation key cellular processes relevant physiology such as stability, subcellular localization, enzyme activity, transcriptional protein-protein interactions protein-DNA interactions. Herein, we summarize functional diversity mechanisms eight kinds nonhistone physiological progression several We highlight recent development inhibitors for acyltransferase, deacylase, reader proteins their potential applications drug discovery.

Язык: Английский

Процитировано

97

Degrader-antibody conjugates DOI
Peter S. Dragovich

Chemical Society Reviews, Год журнала: 2022, Номер 51(10), С. 3886 - 3897

Опубликована: Янв. 1, 2022

This review illustrates the design of antibody conjugates which employ chimeric protein degraders ( i.e. , PROTACs) as payloads and summarizes examples such entities that are currently known in scientific patent literature.

Язык: Английский

Процитировано

90

The state of the art of PROTAC technologies for drug discovery DOI
Chao Wang,

Cangxin Zheng,

Han Wang

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2022, Номер 235, С. 114290 - 114290

Опубликована: Март 15, 2022

Язык: Английский

Процитировано

86

Strategies for designing proteolysis targeting chimaeras (PROTACs) DOI
Shipeng He, Guoqiang Dong,

Junfei Cheng

и другие.

Medicinal Research Reviews, Год журнала: 2022, Номер 42(3), С. 1280 - 1342

Опубликована: Янв. 10, 2022

Abstract Proteolysis targeting chimaeras (PROTACs) is a cutting edge and rapidly growing technique for new drug discovery development. Currently, the largest challenge in molecular design development of PROTACs efficient identification potent drug‐like degraders. This review aims to comprehensively summarize analyse state‐of‐the‐art methods strategies PROTACs. We provide detailed illustration general principles tactics designing PROTACs, highlight representative case studies, discuss advantages limitations these strategies. Particularly, structure‐based rational PROTAC emerging types (e.g., homo‐PROTACs, multitargeting photo‐control PROTAC‐based conjugates) will be focused on.

Язык: Английский

Процитировано

74