Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules

被引：10

作者：

Delport, Alexandre ^{[1
]}

Hewer, Raymond ^{[1
]}

机构：

[1] Univ KwaZulu Natal, Sch Life Sci, Discipline Biochem, ZA-3201 Pietermaritzburg, South Africa

来源：

MOLECULES | 2019年 / 24卷 / 18期

基金：

新加坡国家研究基金会;

关键词：

PROTACs; SNIPERs; targeted protein degradation; drug development; CHAPERONE-MEDIATED AUTOPHAGY; SELECTIVE DEGRADATION; UBIQUITIN LIGASES; TARGET PROTEINS; KNOCKDOWN; PROTAC; RECEPTOR; DESIGN; INHIBITOR; CANCER;

D O I：

10.3390/molecules24183272

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Current drug development strategies that target either enzymatic or receptor proteins for which specific small molecule ligands can be designed for modulation, result in a large portion of the proteome being overlooked as undruggable. The recruitment of natural degradation cascades for targeted protein removal using heterobifunctional molecules (or degraders) provides a likely avenue to expand the druggable proteome. In this review, we discuss the use of this drug development strategy in relation to degradation cascade-recruiting mechanisms and successfully targeted disease-related proteins. Essential characteristics to be considered in degrader design are deliberated upon and future development challenges mentioned.

引用

页数：18

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