JQ-1

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.

A photocaged dibenzosilacycloheptyne (photo-DBSH) and the complementary azide were deployed to tag the oncoprotein ligands (i.e., (+)-JQ1 for BRD4 and Olaparib for PARP1) and the E3 ligase ligand (i.e., Pomalidomide for CRBN), respectively, for a proof-of-concept study and potential treatment for triple-negative breast cancer (TNBC). Further in zebrafish models, PCPTAC promoted BRD4 degradation leading to thinner yolk sac extension and achieved 94% tumor inhibition in HeLa xenografts. This split-and-photoclick strategy paves a new avenue for developing safer and more efficacious PROTACs with synergistic antitumor effects.

The effects of JQ1‑mediated BRD4 and A‑485‑mediated p300 inhibition were assessed using cell viability and colony formation assays...However, deacetylation of  individual enhancer regions using CRISPR was insufficient to fully suppress KLF6 transcription, emphasizing the robustness of the KLF6 SE and its modular role in sustaining high KLF6 expression. Overall, the present study deepens the understanding of growth‑promoting KLF6 transcriptional networks in ccRCC and offers insights to support the development of diagnostic or therapeutic strategies.

In this study, we designed and synthesized a series of compounds derived from the histone deacetylase inhibitor (HDACi) Chidamide and the BET bromodomain inhibitor (+)-JQ-1. In the chicken embryo chorioallantoic membrane (CAM) model, 6e inhibited tumor growth and angiogenesis more effectively than chidamide. In summary, 6e demonstrates promising optimization potential as a lead compound for breast cancer therapy.

We tested these bifunctionals in a FKBP(F36V)-tagged transcription factor reporter system and found bifunctional induced transactivation is relatively common, being observed for bifunctionals with BET ligand JQ1, p300/CBP ligand GNE-781, CDK9 ligand SNS-032, and BRD9 ligand iBRD9. Together, these data establish bifunctionals targeting p300/CBP that toggle between a program of ultra-potent transactivation and repression depending on cellular context. Overall demonstrating that induced proximity with a given ligand does not encode a fixed functional outcome.

In this study, we designed a temperature-tunable photothermal immunotherapy hydrogel dressing (Pd/JQ1@SerMA) to overcome these melanoma postoperative complications...Notably, the hydrogel adaptively fills irregular wound defects, and accelerates postoperative tissue regeneration under mild photothermal stimulation (~ 42 °C). In conclusion, this temperature-tunable photothermal immunotherapeutic hydrogel exhibits remarkable clinical potential for preventing tumor recurrence, combating infection, and promoting wound healing.

Three genes (MXRA7, PLEKHG4B and ATP2B4) were identified to construct a SERG-related model in BLCA, which provides a basis for understanding BLCA pathogenesis and new insights into BLCA treatment.

When appended to the BET bromodomain inhibitor JQ1, this optimized handle yielded a potent and selective BRD4 degrader whose activity was dependent on RNF126. Importantly, transplantation of this handle onto a previously non-inhibitory ligand targeting the androgen receptor (AR) and its truncation variant, AR-V7, enabled selective degradation of both AR and AR-V7 in androgen-independent prostate cancer cells, thereby robustly inhibiting AR transcriptional activity beyond the established AR antagonist enzalutamide. Collectively, these findings demonstrate an optimized RNF126-based covalent handle for the rational development of molecular glue degraders against transcriptional regulators, including undruggable variants such as AR-V7.