PROTACs: past, present and future

K Li, CM Crews - Chemical Society Reviews, 2022 - pubs.rsc.org
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules consisting of
one ligand that binds to a protein of interest (POI) and another that can recruit an E3 …

[HTML][HTML] PROTAC targeted protein degraders: the past is prologue

M Békés, DR Langley, CM Crews - Nature Reviews Drug Discovery, 2022 - nature.com
Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …

[HTML][HTML] A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo

C Kofink, N Trainor, B Mair, S Wöhrle, M Wurm… - Nature …, 2022 - nature.com
Targeted protein degradation offers an alternative modality to classical inhibition and holds
the promise of addressing previously undruggable targets to provide novel therapeutic …

Recent developments in PROTAC‐mediated protein degradation: from bench to clinic

Z Hu, CM Crews - ChemBioChem, 2022 - Wiley Online Library
Abstract Proteolysis‐targeting chimeras (PROTACs), an emerging paradigm‐shifting
technology, hijacks the ubiquitin‐proteasome system for targeted protein degradation …

Degrader-antibody conjugates

PS Dragovich - Chemical Society Reviews, 2022 - pubs.rsc.org
Degrader-antibody conjugates (DACs) are novel entities that combine a proteolysis
targeting chimera (PROTAC) payload with a monoclonal antibody via some type of chemical …

[HTML][HTML] From conception to development: investigating PROTACs features for improved cell permeability and successful protein degradation

C Cecchini, S Pannilunghi, S Tardy… - Frontiers in …, 2021 - frontiersin.org
Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional degraders that
specifically eliminate targeted proteins by hijacking the ubiquitin-proteasome system (UPS) …

Direct-to-biology accelerates PROTAC synthesis and the evaluation of linker effects on permeability and degradation

CE Hendrick, JR Jorgensen, C Chaudhry… - ACS medicinal …, 2022 - ACS Publications
A platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) has been
developed using a direct-to-biology (D2B) approach with a focus on linker effects. A large …

PROTAC degraders as chemical probes for studying target biology and target validation

V Němec, MP Schwalm, S Müller… - Chemical Society Reviews, 2022 - pubs.rsc.org
Small molecule degraders such as PROTACs (PROteolysis TArgeting Chimeras) have
emerged as new promising pharmacological modalities and the first PROTAC drug …

Amide-to-ester substitution as a strategy for optimizing PROTAC permeability and cellular activity

VG Klein, AG Bond, C Craigon… - Journal of medicinal …, 2021 - ACS Publications
Criteria for predicting the druglike properties of “beyond Rule of 5” Proteolysis Targeting
Chimeras (PROTAC) degraders are underdeveloped. PROTAC components are often …

Discovery of sulanemadlin (ALRN-6924), the first cell-permeating, stabilized α-helical peptide in clinical development

V Guerlavais, TK Sawyer, L Carvajal… - Journal of Medicinal …, 2023 - ACS Publications
We report the discovery of sulanemadlin (ALRN-6924), the first cell-permeating, stabilized α-
helical peptide to enter clinical trials. ALRN-6924 is a “stapled peptide” that mimics the N …