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 …

Current advances of small molecule E3 ligands for proteolysis-targeting chimeras design

D Mi, Y Li, H Gu, Y Li, Y Chen - European Journal of Medicinal Chemistry, 2023 - Elsevier
Proteolysis-targeting chimeras (PROTACs) as an emerging drug discovery modality has
been extensively concerned in recent years. Over 20 years development, accumulated …

Discovery of potent and selective WDR5 proteolysis targeting chimeras as potential therapeutics for pancreatic cancer

X Yu, D Li, J Kottur, HS Kim, LE Herring… - Journal of Medicinal …, 2023 - ACS Publications
As a core chromatin-regulatory scaffolding protein, WDR5 mediates numerous protein–
protein interactions (PPIs) with other partner oncoproteins. However, small-molecule …

Luciferase-and HaloTag-based reporter assays to measure small-molecule-induced degradation pathway in living cells

MP Schwalm, K Saxena, S Müller, S Knapp - Nature Protocols, 2024 - nature.com
The rational development of small-molecule degraders (eg, proteolysis targeting chimeras)
remains a challenge as the rate-limiting steps that determine degrader efficiency are largely …

Recent advances in developing degraders & inhibitors of lysine methyltransferases

J Velez, HÜ Kaniskan, J Jin - Current Opinion in Chemical Biology, 2023 - Elsevier
Over the last several decades, there has been continued interest in developing novel
therapeutic approaches targeting protein lysine methyltransferases (PKMTs). Along with …

Discovery of novel BTK PROTACs with improved metabolic stability via linker rigidification strategy

S Chen, Z Chen, L Lu, Y Zhao, R Zhou, Q Xie… - European Journal of …, 2023 - Elsevier
Abstract Bruton's Tyrosine Kinase (BTK) functions as a key regulator of B-cell receptor (BCR)
signaling pathway, which is frequently hyperactivated in a variety of lymphoma cancers …

Chemically induced degradation of epigenetic targets

M Kabir, X Yu, HÜ Kaniskan, J Jin - Chemical Society Reviews, 2023 - pubs.rsc.org
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules that
induce the ternary complex formation between a protein-of-interest (POI) and an E3 ligase …

PROTAC-Based Protein Degradation as a Promising Strategy for Targeted Therapy in Sarcomas

C Mancarella, A Morrione, K Scotlandi - International Journal of …, 2023 - mdpi.com
Sarcomas are heterogeneous bone and soft tissue cancers representing the second most
common tumor type in children and adolescents. Histology and genetic profiling discovered …

Chemical inhibitors targeting histone methylation readers

X Huang, Y Chen, Q Xiao, X Shang, Y Liu - Pharmacology & Therapeutics, 2024 - Elsevier
Histone methylation reader domains are protein modules that recognize specific histone
methylation marks, such as methylated or unmethylated lysine or arginine residues on …

Recent Progress in Modulation of WD40-Repeat Domain 5 Protein (WDR5): Inhibitors and Degraders

R Gurung, D Om, R Pun, S Hyun, D Shin - Cancers, 2023 - mdpi.com
Simple Summary WD40-repeat (WDR) domain proteins play a crucial role in mediating
protein–protein interactions that sustain oncogenesis in human cancers. WDR5 has two …