Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Undruggable proteins are a class of proteins that are often characterized by large, complex
structures or functions that are difficult to interfere with using conventional drug design …
structures or functions that are difficult to interfere with using conventional drug design …
Recent Progress in Modulation of WD40-Repeat Domain 5 Protein (WDR5): Inhibitors and Degraders
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 …
protein–protein interactions that sustain oncogenesis in human cancers. WDR5 has two …
Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization
The multi-step degradation process of PROteolysis TArgeting Chimeras (PROTACs) poses a
challenge for their rational development, as the rate-limiting steps that determine PROTACs …
challenge for their rational development, as the rate-limiting steps that determine PROTACs …
Discovery of potent small-molecule inhibitors of WDR5-MYC interaction
WD repeat domain 5 (WDR5) is a member of the WD40-repeat protein family that plays a
critical role in multiple processes. It is also a prominent target for pharmacological inhibition …
critical role in multiple processes. It is also a prominent target for pharmacological inhibition …
Unannotated microprotein EMBOW regulates the interactome and chromatin and mitotic functions of WDR5
The conserved WD40-repeat protein WDR5 interacts with multiple proteins both inside and
outside the nucleus. However, it is currently unclear whether and how the distribution of …
outside the nucleus. However, it is currently unclear whether and how the distribution of …
Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models
KB Teuscher, S Chowdhury… - Proceedings of the …, 2023 - National Acad Sciences
WD repeat domain 5 (WDR5) is a core scaffolding component of many multiprotein
complexes that perform a variety of critical chromatin-centric processes in the nucleus …
complexes that perform a variety of critical chromatin-centric processes in the nucleus …
Discovery of potent and selective WDR5 proteolysis targeting chimeras as potential therapeutics for pancreatic cancer
As a core chromatin-regulatory scaffolding protein, WDR5 mediates numerous protein–
protein interactions (PPIs) with other partner oncoproteins. However, small-molecule …
protein interactions (PPIs) with other partner oncoproteins. However, small-molecule …
Discovery and structure-based design of inhibitors of the WD repeat-containing protein 5 (WDR5)–MYC interaction
WDR5 is a critical chromatin cofactor of MYC. WDR5 interacts with MYC through the WBM
pocket and is hypothesized to anchor MYC to chromatin through its WIN site. Blocking the …
pocket and is hypothesized to anchor MYC to chromatin through its WIN site. Blocking the …
Discovery of potent orally bioavailable WD repeat domain 5 (WDR5) inhibitors using a pharmacophore-based optimization
WD repeat domain 5 (WDR5) is a nuclear scaffolding protein that forms many biologically
important multiprotein complexes. The WIN site of WDR5 represents a promising …
important multiprotein complexes. The WIN site of WDR5 represents a promising …
WIN site inhibition disrupts a subset of WDR5 function
AJ Siladi, J Wang, AC Florian, LR Thomas… - Scientific Reports, 2022 - nature.com
WDR5 nucleates the assembly of histone-modifying complexes and acts outside this context
in a range of chromatin-centric processes. WDR5 is also a prominent target for …
in a range of chromatin-centric processes. WDR5 is also a prominent target for …