May 9, 2023 · In this study, we employed a BRD4-targeting PROTAC molecule to regulate the super-enhancer (SE) condensate and monitored the changes of SE condensate under PROTAC treatment using live-cell...

Oct 30, 2024 · Proteolytic targeting chimera (PROTAC) represent an advanced strategy for targeting undruggable proteins, and the molecular warheads targeting E3 ligases play a crucial role. Recently, we explored an alkenyl oxindole warhead targeting the E3 ligase DCAF11 and sought to validate its potential.

Jan 5, 2022 · In this study, we designed and synthesized a series of PROTACs based on our recently reported dual BET/PLK1 inhibitor WNY0824, which led to the discovery of an isoform-selective and potent BRD4-PROTAC 12a (WWL0245).

Aug 20, 2024 · We demonstrated that 6b (BRD4 PROTAC) suppresses BLBC cell growth by targeting BRD4, but not BRD2 and BRD3, for cereblon (CRBN)-mediated ubiquitination and proteasomal degradation.

Mar 13, 2017 · We solved the crystal structure of Brd4 degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4 BD2). The ligand folds into itself to allow formation of specific intermolecular...

Dec 17, 2024 · We present a suite of BRD4 PROTAC degraders prepared via four new amine–acid coupling reactions alongside the classic amide coupling. Our findings reveal that variations in reaction conditions affect the physicochemical properties of PROTACs, resulting in a spectrum of properties.

2 days ago · BRD4 plays a crucial role in transcription regulation in cancer 21, and inhibition of BRD4 can pharmacologically modulate Myc transcriptional function 57, ... Furthermore, similar to BRD4, the PROTAC and MPL (SS) P@SIS nanocapsules both downregulated RAD51AP1 in a dose-dependent way in vitro, according to the WB assays (Fig. 4 F and G).

Sep 26, 2024 · BRD4 binds to acetylated histones through its bromodomains and recruits p-TEFb to facilitate active transcription. BRD4 is an attractive target for PROTAC-mediated degradation because BRD degradation results in more enhanced cancer cell death compared with its inhibition by small compounds.

4 days ago · Patent WO 2024/175905 A1 PROTAC Compounds Targeting BRD4, BTK, and AR: This patent introduces PROTAC (Proteolysis Targeting Chimera) technology to selectively degrade oncogenic proteins such as BRD4, BTK, and AR, which are implicated in prostate cancer and hematological malignancies. PROTAC compounds are designed to …

This work introduces a targeting drug delivery system (SPP-ARV-825) consisting of mPEG-PDLLA, SP-PEG-PDLLA and BRD4 PROTAC drug ARV-825 for glioma therapy. The SPP-ARV-825 efficiently induces BRD4 degradation and attenuates glioma tumor growth.