Description
Product Usage Information
MZ1 is supplied as a lyophilized powder. For a 5 mM stock, reconstitute 5 mg of powder in 997 μL of DMSO. Working concentrations and length of treatment can vary depending on the desired effect.
Storage
Store lyophilized at -20ºC, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 2 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles .
Background
The MZ1 compound is a proteolysis-targeting chimera (PROTAC) degrader of bromodomain-containing protein 4 (BRD4) (1). MZ1 is composed of a bromodomain inhibitor (JQ1) bound to a ligand that recruits the von Hippel-Lindau (VHL) E3 ubiquitin ligase (1). This ligase is part of a complex that works to regulate the cellular response to oxygen levels and target specific proteins for degradation (2). By binding to this ligase and then to BRD4 bromodomains, MZ1 tags the protein for degradation (1). The BRD4 protein is an epigenetic regulator involved in gene expression and transcription regulation, often found to be overactive in several cancers, including breast and leukemias (3). The ability of BRD4 to attach to acetylated histones at promoters and enhancers is a focus in clinical research, as these actions can drive uncontrolled cancer growth (3). MZ1 has also been shown to exert anticancer effects in acute myeloid leukemia (AML), as BRD4 degradation leads to c-Myc downregulation, which is critical for AML survival (4). The median IC for BRD4 is 49 nM. It is effective at lower concentrations ranging from 5 to 150 nM (5).
