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...

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).

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.

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.

Oct 1, 2019 · ARV-825 (ARV), a molecule designed using PROteolysis-TArgeting Chimeric (PROTAC) technology, degrades BRD4 protein instead of merely inhibiting it. Based on extensive preformulation studies, ARV loaded self-nanoemulsifying preconcentrate (ARV-SNEP) was developed and optimized.

12a (WWL0245) is a potent and highly selective BRD4-PROTAC. 12a exhibited better antiproliferative activity in AR-positive prostate cancer cells than WNY0824. BRD4-targeted proteolysis targeting chimera (PROTAC) have exhibited promising in vitro and in vivo anticancer activity in a number of cancer models.

MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML.

In 2018, Qin et al. also disclosed a new BRD4 PROTAC (PROTAC 4, Figure 4), derived from BRD4 inhibitor QCA-276 and CRBN ligand lenalidomide 41. PROTAC 4 was the most potent BRD4 degrader reported to date, potently degrading BRD4 at picomolar concentrations.