Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules

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 prot...

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Bibliographic Details
Main Authors:	Alexandré Delport, Raymond Hewer
Format:	Article
Language:	English
Published:	MDPI AG 2019-09-01
Series:	Molecules
Subjects:	PROTACs SNIPERs targeted protein degradation drug development
Online Access:	https://www.mdpi.com/1420-3049/24/18/3272

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spelling	doaj-8459efa42a2b4d12a5d521d3652cd2f22020-11-24T21:28:22ZengMDPI AGMolecules1420-30492019-09-012418327210.3390/molecules24183272molecules24183272Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional MoleculesAlexandré Delport0Raymond Hewer1Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg 3201, South AfricaDiscipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg 3201, South AfricaCurrent 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.https://www.mdpi.com/1420-3049/24/18/3272PROTACsSNIPERstargeted protein degradationdrug development
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Alexandré Delport Raymond Hewer
spellingShingle	Alexandré Delport Raymond Hewer Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules Molecules PROTACs SNIPERs targeted protein degradation drug development
author_facet	Alexandré Delport Raymond Hewer
author_sort	Alexandré Delport
title	Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules
title_short	Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules
title_full	Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules
title_fullStr	Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules
title_full_unstemmed	Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules
title_sort	inducing the degradation of disease-related proteins using heterobifunctional molecules
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-09-01
description	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.
topic	PROTACs SNIPERs targeted protein degradation drug development
url	https://www.mdpi.com/1420-3049/24/18/3272
work_keys_str_mv	AT alexandredelport inducingthedegradationofdiseaserelatedproteinsusingheterobifunctionalmolecules AT raymondhewer inducingthedegradationofdiseaserelatedproteinsusingheterobifunctionalmolecules
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Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules

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