Discovery of a novel, highly potent EZH2 PROTAC ... - ScienceDirect
Mar 5, 2024 · Here we present MS8847, a novel, highly potent EZH2 PROTAC degrader that recruits the E3 ligase von Hippel-Lindau (VHL). MS8847 degrades EZH2 in a concentration-, time-, and ubiquitin–proteasome system (UPS)-dependent manner.
Discovery of a novel, highly potent EZH2 PROTAC degrader for …
Here we present MS8847, a novel, highly potent EZH2 PROTAC degrader that recruits the E3 ligase von Hippel-Lindau (VHL). MS8847 degrades EZH2 in a concentration-, time-, and ubiquitin–proteasome system (UPS)-dependent manner.
EZH2 noncanonically binds cMyc and p300 through a cryptic
Feb 24, 2022 · To suppress the multifaceted activities of EZH2, we used proteolysis-targeting chimera (PROTAC) to develop a degrader, MS177, which achieved effective, on-target depletion of EZH2 and...
Discovery of a first-in-class EZH2 selective degrader
Dec 9, 2019 · Using a hydrophobic tagging approach, we generated MS1943, a first-in-class EZH2 selective degrader that effectively reduces EZH2 levels in cells.
Design and Synthesis of EZH2-Based PROTACs to Degrade the …
Feb 19, 2021 · EZH2 mediates both PRC2-dependent gene silencing via catalyzing H3K27me3 and PRC2-independent transcriptional activation in various cancers. Given its oncogenic role in cancers, EZH2 has constituted a compelling target for anticancer therapy.
Discovery of a novel, highly potent EZH2 PROTAC degrader for
Mar 5, 2024 · Here we present MS8847, a novel, highly potent EZH2 PROTAC degrader that recruits the E3 ligase von Hippel-Lindau (VHL). MS8847 degrades EZH2 in a concentration-, time-, and ubiquitin-proteasome system (UPS)-dependent manner.
Novel Protac-Based EZH2 Degraders Effectively Target EZH2 …
Nov 2, 2023 · EZH2 PROTAC treatment reduces the transcription levels of these oncogenes corroborating with loss of c-Myc protein expression. Studying the pharmacokinetics of the lead PROTACs in a mouse model revealed good plasma stability, half-life (> 4 h), and low clearance.
Design, synthesis and evaluation of EZH2-based PROTACs
In our study, compound E-3P-MDM2 is the most active PROTAC molecule. It degraded EZH2 of the SU-DHL-6 cells in a concentration and dose-dependent manner and also degraded both EED and SUZ12 protein without affecting their mRNA levels, then …
Novel Protac-Based EZH2 Degraders Effectively Target EZH2 …
Nov 2, 2023 · EZH2 PROTAC treatment reduces the transcription levels of these oncogenes corroborating with loss of c-Myc protein expression. Studying the pharmacokinetics of the lead PROTACs in a mouse model revealed good plasma stability, half-life (> 4 h), and low clearance.
EZH2 PROTACs target EZH2- and FOXM1-associated oncogenic …
Aug 7, 2024 · Unlike methyltransferase inhibitors, proteolysis targeting chimeras (PROTAC) can suppress both activating and repressive functions of EZH2.