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 imaging and high-throughput sequencing technologies. As a result, we found that BRD4-targeting PROTACs can ...
Biomolecular condensates play key roles in various biological processes. However, specific condensation modulators are currently lacking. PROTAC is a new technology that can use small molecules to degrade target proteins specifically. PROTAC molecules ar
peaks of H3K27ac were obtained in M2 macrophages; among those, 96.4% of peaks were overlapped, which was slightly higher as in M0 (Fig.5a). Peaks were widely distributed across the genome, including promoter, introns, and distal intergenic regions. Originally, around 25% of BRD4 and H3K27...
To investigate the potency of PROTAC-induced BRD4 degradation, LS174t cells were treated with either dBET1 or MZ1 for 24 h. Both PROTACs lead to complete degradation of BRD4 protein, whereas the expression of BRD4 mRNA was not reduced (Figure 2B, C). Notably, both PROTACs demonstrated ...
- and apoptosis regulators (Bcl-2, Bcl-XL , etc .) and has been validated as a target in AML therapy1 . ARV-825 is a hetero-bifunctional PROteolysis TArgeting Chimera (PROTAC) that recruits BRD4 to the E3 ubiquitin ligase cereblon and leads to efficient and sustained degradation of BRD4 ...
BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3doi:10.1080/16078454.2023.2247253BET inhibitorBRD4MZ1B-cell acute lymphoblastic leukemiaCCND3Introduction B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting ...
PROTACTargeted protein degradationUbiquitin-proteasome systemRationale: Proteolysis Targeting Chimeras (PROTACs) are bifunctional compounds that have been extensively studied for their role in targeted protein degradation (TPD). The capacity to degrade validated or undruggable targets provides PROTACs...
ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell...
Most importantly, significant reduction in the growth of multicellular 3D spheroid of A549 cells confirmed the effectiveness of BRD4 PROTAC and its lipid nanoparticle in non-small cell lung cancer (NSCLC). AP-NLC. Higher amount of red fluorescence throughout the spheroid surface further confirmed...
Polo-like kinase 1 (PLK1) and bromodomain 4 (BRD4) are both attractive therapeutic targets in acute myeloid leukemia (AML). Here, we developed a small-molecule BRD4 and PLK1 degrader HBL-4 based on PROTAC technology, which leads to fast, efficient, and prolonged degradation of BRD4 and ...