A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders

Fischer, Patrick D.; Papadopoulos, Evangelos; Dempersmier, Jon; Wang, Zifu; Nowak, Radosław P.; Donovan, Katherine A.; Kalabathula, Joann; Gorgulla, Christoph; Junghanns, Pierre; Kabha, Eihab; Dimitrakakis, Nikolaos; Petrov, Ognyan; Mitsiades, Constantine S.; Ducho, Christian; Gelev, Vladimir; Fischer, Eric S.; Wagner, Gerhard; Arthanari, Haribabu

doi:10.1016/j.ejmech.2021.113435

Cited by 17 publications

(12 citation statements)

References 56 publications

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“…3d), resulting in improved cellular uptake. 18 Collectively, these findings suggested that using lipophilic groups to mask the key polar motifs through cleavable bonds could be adapted as a facile and straightforward strategy to improve the unfavorable cell permeability and other pharmacokinetic properties.…”

Section: Prodrugsmentioning

confidence: 99%

Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation

et al. 2022

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Section: Prodrugsmentioning

confidence: 99%

Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation

et al. 2022

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“…26). 136 Interestingly, even though 4E-BP1 and eIF4G contain the same binding motif, 4EGI-1 (101) and i4EG-BiP (103) can only displace eIF4G and not 4E-BP1 in cells.…”

Section: Eif4e Degradation Approachesmentioning

confidence: 99%

Medicinal chemistry approaches to target the MNK–eIF4E axis in cancer

et al. 2023

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“… 61 Then they designed and synthesized a series of eIF4E degraders based on the binding mode of i4EG-BiP and eIF4E. 62 Through the degradation activity test, it was found that the degrader 32 ( d4E-4 , Fig. 8 ) and the degrader 33 ( d4E-6 , Fig.…”

Section: Protacs Targeting Cancer-related Targetsmentioning

confidence: 99%

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

Cao

et al. 2022

Sig Transduct Target Ther

111

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PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin–proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article “PROTACs: great opportunities for academia and industry” in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020–2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.

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A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders

Cited by 17 publications

References 56 publications

Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation

Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation

Medicinal chemistry approaches to target the MNK–eIF4E axis in cancer

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

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