JQ-1

The combination of chemotherapy and immune checkpoint blockade therapy shows great potential in tumor treatment, but their integration remains a great challenge. Meanwhile‌, overexpression of programmed cell death ligand 1 (PD-L1) is suppressed by JQ1, thereby reversing PD-L1-mediated immune resistance to synergistically promote adaptive antitumor immune response. This hypoxia-sensitive versatile nanoplatform provides an elegant paradigm for precise tumor therapy.

Among them, TRIB2 was distinguished by its SE recurrence, tumour overexpression, prognostic value and JQ-1 suppression. The SEFG signature facilitates simultaneous prediction of prognosis and assessment of the immune microenvironment, providing a potential tool for colon cancer management.

JQ1 treatment significantly repressed these tumor-specific pathways, suggesting a therapeutic potential for targeting SE-driven transcription in HPV+ HNSCC. This study underscores the critical role of SEs in epigenetic and transcriptional dysregulation in HPV+ HNSCC, revealing therapeutic targets and providing a framework for future mechanistic studies in this area.

Interestingly, JQ1 (a specific BET inhibitor) triggered cell cycle arrest only in sensitive cells when used alone while addition of mTOR inhibitors extended this antiproliferative effect to BET-resistant cells as well...This study validates the combined use of BET and mTOR inhibitors as a promising treatment strategy for AML, capable of overcoming resistance and enhancing therapeutic outcomes. Furthermore, our investigation also highlights EGR1 not only as a biomarker of treatment response, but also as a potential target for future therapeutic interventions, offering valuable insights for patient management.

In this study, we demonstrate that the BET inhibitor JQ1 induces the upregulation of Thioredoxin Interacting Protein (TXNIP), which mediates the anti-tumor effects of JQ1...Nevertheless, these quiescent cells exhibit sensitivity to ferroptosis, suggesting that BET inhibitors enhance the anti-tumor efficacy of ferroptosis inducers. Collectively, our findings elucidate the regulators of protein UFMylation and cMYC activity, which modulate cellular responses to BET inhibitors and ferroptosis inducers in solid cancer cells.

Genetic or pharmacological degradation of RBM39 (using the clinically explored molecular glue indisulam) potently reactivates latent HIV-1 in J-Lat cell models, primary CD4⁺ T cells from people living with HIV-1 (PLWH), and synergizes with established LRAs (Bryostatin-1, JQ-1, SAHA) to broadly activate proviral reservoirs...In addition to establishing RBM39 as a promising therapeutic target for addressing the limitations of current "shock and kill" strategies, our findings establish a novel mechanistic framework for m⁶A-dependent regulation of viral gene expression. This framework may serve as a valuable reference for investigating similar regulatory mechanisms in other latent viral infections or oncogenic processes where RNA methylation plays a pivotal role.

D463H expression reduced the sensitivity of cells to the BET inhibitors JQ1 and AZD5153, indicating the functional importance of these pathways. The findings indicate that D463H is a dominant gain-of-function oncogenic mutant that operates through a noncatalytic allosteric mechanism.

Herein, we designed, synthesized and evaluated bromodomain 4 (BRD4)-targeting PROTACs (BRD4-PROTACs) that employ a well-known BRD4 inhibitor (JQ1) as a warhead and Vpr-derived peptides as the E3 ligase-binding ligands...The chemical degraders are less effective than the parent inhibitor as a latency-reversing agent (LRA). However, the low cytotoxicity of the new peptidic PROTACs allowed the compounds to be tolerated at high does, leading to potent LRA activity.

The antiproliferative effects of JQ1 and vincristine were comparable, and there was trend towards reduced and delayed xenograft growth in JQ1-treated mice. We conclude that confirmatory preclinical trials allow for robust assessment of the efficacy of candidate interventions and reduce bias in academic research. The study platform established here provides a framework that may be of particular benefit for the development of new drugs for rare cancers.

In addition, downregulation of BRD4 using siRNA and JQ1 led to decreases in the protein levels of BRD4 and c-Myc...These findings suggested that CENP-F regulated the proliferation of HCC cells through the CENP-F-CDK1/CDK2-BRD4 axis. In conclusion, our study revealed a new mechanism by which CENP-F promotes HCC cell proliferation by the SE reader BRD4, suggesting that SEs play an essential role in mediating HCC treatment.

BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.

We evaluated the effects of the CDK4/6 inhibitor palbociclib (PD-0332991) and the bromodomain and extra-terminal (BET) inhibitor JQ1, administered individually and in combination, on human PDAC cell lines in vitro and on tumor growth in an orthotopic mouse model. Combined inhibition of CDK4/6 and BET produced a synergistic antitumor effect in vitro and in vivo. Our findings support a combined therapeutic strategy targeting CDK4/6 and BET proteins to achieve synergistic inhibition of PDAC progression.