Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets
Ubiquitin–proteasome system (UPS) is a primary signaling pathway for regulation of intracellular protein levels. E3 ubiquitin ligases, substrate-specific members of the UPS, represent highly attractive protein targets for drug discovery. The importance of E3 ligases as prospective targets for small...
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doaj-3eda039980734e2dbf6eb0aff16bb3742020-11-24T23:15:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-05-01910.3389/fphar.2018.00450344951Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as TargetsEmil Bulatov0Almaz Zagidullin1Aygul Valiullina2Regina Sayarova3Albert Rizvanov4Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, RussiaA.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, RussiaUbiquitin–proteasome system (UPS) is a primary signaling pathway for regulation of intracellular protein levels. E3 ubiquitin ligases, substrate-specific members of the UPS, represent highly attractive protein targets for drug discovery. The importance of E3 ligases as prospective targets for small molecule modulation is reinforced by ever growing evidence of their role in cancer and other diseases. To date the number of potent compounds targeting E3 ligases remains rather low and their rational design constitutes a challenging task. To successfully address this problem one must take into consideration the multi-subunit nature of many E3 ligases that implies multiple druggable pockets and protein–protein interfaces. In this review, we briefly cover the current state of drug discovery in the field of RING-type E3 ligases with focus on MDM and Cullin families as targets. We also provide an overview of small molecule chimeras that induce RING-type E3-mediated proteasomal degradation of substrate proteins of interest.http://journal.frontiersin.org/article/10.3389/fphar.2018.00450/fullubiquitin–proteasome systemRING-type E3 ligasesMDM familyCullin familysmall moleculesinduced protein degradation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emil Bulatov Almaz Zagidullin Aygul Valiullina Regina Sayarova Albert Rizvanov |
spellingShingle |
Emil Bulatov Almaz Zagidullin Aygul Valiullina Regina Sayarova Albert Rizvanov Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets Frontiers in Pharmacology ubiquitin–proteasome system RING-type E3 ligases MDM family Cullin family small molecules induced protein degradation |
author_facet |
Emil Bulatov Almaz Zagidullin Aygul Valiullina Regina Sayarova Albert Rizvanov |
author_sort |
Emil Bulatov |
title |
Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets |
title_short |
Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets |
title_full |
Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets |
title_fullStr |
Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets |
title_full_unstemmed |
Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets |
title_sort |
small molecule modulators of ring-type e3 ligases: mdm and cullin families as targets |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2018-05-01 |
description |
Ubiquitin–proteasome system (UPS) is a primary signaling pathway for regulation of intracellular protein levels. E3 ubiquitin ligases, substrate-specific members of the UPS, represent highly attractive protein targets for drug discovery. The importance of E3 ligases as prospective targets for small molecule modulation is reinforced by ever growing evidence of their role in cancer and other diseases. To date the number of potent compounds targeting E3 ligases remains rather low and their rational design constitutes a challenging task. To successfully address this problem one must take into consideration the multi-subunit nature of many E3 ligases that implies multiple druggable pockets and protein–protein interfaces. In this review, we briefly cover the current state of drug discovery in the field of RING-type E3 ligases with focus on MDM and Cullin families as targets. We also provide an overview of small molecule chimeras that induce RING-type E3-mediated proteasomal degradation of substrate proteins of interest. |
topic |
ubiquitin–proteasome system RING-type E3 ligases MDM family Cullin family small molecules induced protein degradation |
url |
http://journal.frontiersin.org/article/10.3389/fphar.2018.00450/full |
work_keys_str_mv |
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