JQ-1

Importantly, in vivo studies using a xenograft mouse model demonstrate significant tumor growth inhibition, with the nanoformulation + NIR irradiated group showing the most effective anti-tumor outcome with negligible hepatic, renal, and cardiac toxicities. Taken together, it may be stated that the doxorubicin/JQ1 co-loaded PBNCs might be a potential next-generation anti-TNBC theranostic agent, which combines dual-mode MRI capability and combination therapy with reduced side effects.

In addition, we demonstrate that the first bromodomain of the bromodomain and extraterminal domain-containing protein BRD4 binds to the acetylated region of interest and that this interaction is inhibited through the bromodomain and extraterminal domain inhibitor JQ1. These findings confer molecular mechanistic detail to previous observations that BRD4 and PAX3-FOXO1 colocalize at superenhancers in ARMS, adding to the growing body of literature exploring how BRD4 contacts cancer-relevant transcription factors in ways potentially relevant to the use of bromodomain and extraterminal domain inhibitors in cancer treatment.

Proteomic analysis identified unique protein candidates altered in MZ-1- and SIM-1-treated KSHV-infected immortalized endothelial cells compared with (+)-JQ1-treated cells. In summary, our study develops an effective strategy against KSHV-infected immortalized endothelial cells using selective BRD PROTACs, which may help improve therapeutic outcomes for KSHV-related malignancies in the future.

JQ1 conveniently entered the adjacent cell nucleus and prevented induced PD-L1 production at the transcriptional level...Besides degrading PD-L1, the cholesterol metabolism regulation of AVA could also downregulate integrin αV expression to inhibit tumor metastasis. Therefore, by improving immunogenicity, eliminating immune resistance, and downregulating integrin αV, these synergistic therapeutic strategies efficiently inhibit primary tumor and pulmonary metastasis in orthotopic TNBC.

Concurrently, the degradable MN tip enables sustained release of JQ1, which enhances OA replication, modulates lactic acid levels and PD-L1 expression, thereby reprogramming the immunosuppressive TME to promote T-cell infiltration and cytotoxicity. In murine models, MN-OJ demonstrated potent inhibition of both primary and distal tumors, without systemic toxicity. This innovative platform combines immediate tumor destruction with sustained immune modulation, offering a promising clinical approach for melanoma therapy.

SHP2 overexpression, SHP2 knockdown, and SP1 inhibitor BDR4 inhibitor JQ-1 were used to examine the effects of SHP2, SP1, and BRD4 on macrophage polarization and cancer cell death, migration, and invasion...Additionally, there was an increase in cancer cell invasion, migration, and death. SHP2 in TAMs promotes gastric adenocarcinoma survival by inhibiting P38/ erk1 /SP1/BRD4/STING-induced inflammation and ROS.

Specifically, the c-Myc inhibitor JQ1 and bovine serum albumin (BSA)-decorated nanoparticles loaded with the actin cytoskeleton inhibitor NP-G2-044 (BPG) were encapsulated into a reactive oxygen species (ROS)-sensitive hydrogel (JQ1 + BPG@gel). This hydrogel system improved the anti-recurrence efficacy of CAR-T therapy by 9-fold compared with monotherapy while establishing durable immune surveillance via memory T-cell differentiation within lymphoid organs. This research offers an innovative strategy to improve postoperative tumor cure rates and potentiate CAR-T immunotherapy.

Scirrhous CAFs had heavily acetylated super-enhancers, and therapeutic targeting of super-enhancers by a BET bromodomain inhibitor, mivebresib and JQ-1, markedly decreased their migration-promoting activity. Notably, in scirrhous gastric cancer patients, normal fibroblasts in non-cancerous tissues also had a strong migration-promoting effect. It was suggested that fibroblasts in the non-cancerous tissue of scirrhous gastric patients have already acquired tumor-promoting capacity, forming a stromal field for scirrhous gastric cancer although its spatial extent remains to be solved.

Bromodomain and extraterminal motif (BET) inhibitors, such as JQ1, are promising cancer therapeutics that target epigenetic regulators, particularly BRD4...Collectively, our findings establish BRD2 as a critical mediator of pan-cancer adaptive resistance to BETi and identify NFYA as a novel transcriptional regulator of this process. Co-targeting BRD2 or its regulatory network offers a rational strategy to enhance the durability and efficacy of BET-based therapies.

The BRD4 inhibitor JQ1 reduces eccDNA production, while the HDAC inhibitor TSA induces an increase of eccDNAs...Furthermore, large eccDNA breakpoints are found to be coordinated with TAD boundaries and inclined to align at enhancers and promoters. Our study suggests that eccDNAs are more frequently detected from regulatory regions in the genome, consistent with their generation being associated with enhancer-promoter dynamics.

Preliminary results using JQ1-treated melanoma cells in a mixed lymphocyte-tumor cell culture (MLTC) markedly enhanced TIL proliferation and resulted in a T cell product enriched for CD8+ T cells. These findings reveal how the pleiotropic effects of BETi on melanoma cells broadly boost their immunogenicity towards CD8+ T cells and uncover novel pathways that might be therapeutically exploited to enhance CD8+ T cell-mediated anti-tumor immunity in ex vivo and in vivo approaches to cancer immunotherapy.