May 14, 2022 · MZ1 is a novel BET inhibitor that employs proteolytic-targeting chimera (PROTAC) technology for proteasomal degradation of target proteins and has shown excellent effects in some tumors, but its role in neuroblastoma remains poorly understood.

Dec 31, 2022 · 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.

Immuno-blots of six cell lines, treated for 5 h with either DMSO or different concentrations of the degraders MZ1 and dBet6. MZ 1 is a PROTAC connected by ligands for von Hippel-Lindau and BRD4. MZ 1 potently and rapidly induces reversible, long-lasting, and selective removal of BRD4 over BRD2 and BRD3.

Feb 16, 2024 · In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

MZ1 is a first in class PROTAC (proteolysis-targeting chimeras) that tethers JQ1 to a VHL E3 ubiquitin ligase ligand, aimed at triggering the intracellular destruction of BET proteins. It induces reversible, long-lasting, and preferential removal of BRD4 over BRD2 and BRD3 in cells.

Aug 20, 2024 · In the BLBC xenograft model, MZ1 and ARV-825 improved tumor-targeting ability, leading to enhanced BET degradation, antitumor potency, and decreased toxicity [27]. MS83, by linking KEAP1 ligand,...

Mar 19, 2021 · We observed that the administration of MZ1 augmented the antiproliferative capacity of trastuzumab as a single agent, mainly by inducing DNA damage and apoptosis. This result was confirmed in several cell lines and in an in vivo model.

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...

Mar 20, 2019 · Researchers are hijacking the cell’s protein-disposal system in the fight against Alzheimer’s and intractable cancers. Megan Scudellari writes about biomedical research in Boston, Massachusetts.

MZ1 is a novel inhibitor developed using PROTAC technology, which achieves its inhibition of BRD4 by promoting BRD4 ubiquitination and targeting it for proteasomal degradation. MZ1 has demonstrated significant anti-tumor effects in various types of cancers, including B-ALL , AML , NB , and breast cancer [50–52]. In this study, we utilized ...