The second-generation BRD4 inhibitors are mainly synthesized by proteolysis targeting chimera (PROTAC) technology. This approach implicates the use of a molecule that binds both the protein to be degraded and the E3 ubiquitin ligase. Such bridging between the target protein and E3 ligase mediated by...
significantly impacting quality of life and primarily contributing to organ failure. Organ fibrosis is reported to cause 45% of all-cause mortality worldwide. Despite extensive efforts to develop new antifibrotic drugs, drug discovery has not kept pace with the clinical demand. Currently...
(PROTAC) version of JQ1 that binds to BRD4 and induces BRD4 degradation13. As expected, though dBET1 with increasing concentrations can cause BRD4 degradation, it failed to do that in cells co-transfected with the JAK2-V617F (Fig.6c). Likewise, BRD4 phosphorylation mimic BRD4-Y97E/Y98E ...
At present, there are few reports on the treatment of glioma with BRD4 PROTAC nanodrug. We hope the study will bring forward a novel approach for glioma therapy and provide research basis for clinical drug investigation. Download: Download high-res image (467KB) Download: Download full-size ...
(PROTAC) technology and were tested for many disease treatments [21,22]. Although BRD4 plays a critical role in regulating both M1 and M2 macrophage polarization, they have been reported to be effective in the treatment of tumors by modulating the function of tumor-associated macrophage [23,24...
BMS-986158 has a distinct core structure from the first-generation BET bromodomain inhibitors (Supplementary Fig.1), and binds well with the BRD4 bromodomains. This highly selective compound exhibited strong anti-tumor affects and was tested in phase I/II clinical trial for a number of cancer in...
To further explore the importance of BRD4 in HPV-positive HNSCC, a BRD4 inhibitor, MZ1, was used; this inhibitor is a proteolysis targeting chimera (PROTAC) which causes degradation of the target protein [45]. We selected this inhibitor because the EGFR-overexpressing cells had lower expression...
The BET PROTAC inhibitor GNE-987 displays anti-tumor effects by targeting super-enhancers regulated gene in osteosarcoma Di Wu Hongli Yin Jian Pan BMC Cancer(2024) A phenotypic screening approach to target p60AmotL2-expressing invasive cancer cells ...