The multidimensional biology of SKP2: mechanisms, pathologies, and emerging therapeutic frontiers
Acta Materia MedicaS phase kinase-associated protein 2 (SKP2), the rate-limiting substrate receptor of the SKP1-Cullin1-F-box (SCF) E3 ubiquitin ligase complex, is considered a canonical gatekeeper of cell cycle progression.
Tao Hou +7 more
doaj +1 more source
Computational strategies for PROTAC drug discovery
Acta Materia Medica, 2023 Proteolysis-targeting chimeras (PROTACs), a novel targeted protein degradation technology for potential clinical drug discovery, is composed of a protein-targeting ligand covalently linked to an E3 ligase ligand.
Jia Wu, Wanhe Wang, Chung-Hang Leung
doaj +1 more source
Targeting IRAK4 for Degradation with PROTACs [PDF]
ACS Medicinal Chemistry Letters, 2019 Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) is a key mediator of innate immunity. IRAK4 overactivation is linked with several autoimmune diseases. To date, many IRAK4 inhibitors have been developed to block the protein's kinase activity with the most advanced reaching Phase II clinical trials.
Joao Nunes +9 more
openaire +2 more sources
, 2018 A transcription factor called SALL4 could be the missing link between thalidomide and the limb defects caused by the ...
Borozdin +12 more
core +1 more source
Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase [PDF]
, 2019 The suppressor of cytokine signaling 2 (SOCS2) acts as substrate recognition subunit of a Cullin5 E3 ubiquitin ligase complex. SOCS2 binds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation, yet the molecular ...
Bruno, Elvira +4 more
core +2 more sources
Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV
Nature CommunicationsTargeting host proteins that are crucial for viral replication offers a promising antiviral strategy. We have designed and characterised antiviral PROteolysis TArgeting Chimeras (PROTACs) targeting the human protein cyclophilin A (CypA), a host cofactor ...
Lydia S. Newton +17 more
semanticscholar +1 more source
Science-Business eXchange, 2012 GSK and Yale researchers have announced a collaboration to develop a platform that selectively tags disease-associated proteins with an E3 ubiquitin ligase ligand, thus targeting them to a cell's protein degradation machinery. GSK hopes the platform could be a cornerstone for a new Discovery Performance Unit at the pharma and the partners are aiming to
openaire +1 more source
Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities [PDF]
, 2014 E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success.
Adams J. +31 more
core +5 more sources
PROTAC-PatentDB: A PROTAC Patent Compound Dataset
Scientific DataProteolysis-targeting chimeras (PROTAC) are emerging and promising molecules for targeted protein degradation which have the potential to overcome critical bottlenecks in traditional small molecule drug development. However, the scarcity of publicly available data on molecular compound structures has significantly hindered computational drug discovery ...
Hong Cai +4 more
openaire +2 more sources
Targeting endogenous proteins for degradation through the affinity-directed protein missile system [PDF]
, 2017 Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes.
Fulcher, Luke J. +4 more
core +2 more sources