Description
MZ1 is a hybrid compound that drives the selective proteasomal degradation of bromodomain-containing protein 4 (BRD4). It is characterized as a proteolysis-targeting chimera (PROTAC) and contains JQ-1, which binds bromo- and extra-terminal (BET) proteins, linked to a ligand for the E3 ubiquitin ligase VHL. MZ1 induces the selective degradation of BRD4 in HeLa cells when used at 0.1-0.5 μM. At concentrations of 2-10 μM, MZ1 causes the removal of BRD2, BRD3, and BRD4. BRD protein removal is evident within four hours of adding MZ1 and persists for at least 48 hours, unless MZ1 is removed.
Uses
MZ 1, is a BRD4 protein degrader based on PROTAC technology. The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1.
Definition
ChEBI: MZ1 is an organic molecular entity.
References
[1] MICHAEL ZENGERLE Alessio C Kwok Ho Chan. Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4[J]. ACS Chemical Biology, 2015, 10 8: 1770-1777. DOI:
10.1021/acschembio.5b00216
