BRD4 (Bromodomain Containing 4)

Hence, a deeper investigation into the molecular mechanisms of SPOP in prostate cancer will provide novel insights into its physiological function in oncogenesis and drug development. In this review, we summarize SPOP's tumor suppressor functions and structural features, upstream regulatory mechanisms, and SPOP-targeting therapeutic strategies in prostate cancer.

Genomic data from six cancer types reveals a strong positive ASXL1-BRD4 relationship, with BRD4 occupying the ASXL1 promoter and thus pointing to a possible feed-forward mechanism. Our findings provide mechanistic details by which ASXL1 associates with BRD4 and shed light on the biological significance of this association.

The lead compound, 10k (ZX079), induces potent, dose- and time-dependent degradation of BRD4 and CBP and demonstrates superior suppression of oncogenic transcription and inhibition of AML cell proliferation compared with the dual BET/CBP inhibitor NEO2734. In vivo, 10k significantly reduces tumor growth in an AML xenograft model with TGI over 90%. Collectively, these findings highlight dual degradation of BRD4 and CBP as a promising strategy for AML.

As a result, GA-IS elicits a potent systemic immune response capable of suppressing both primary and metastatic breast cancer, while showing minimal systemic toxicity. This Golgi apparatus-targeting immunostimulant represents a promising strategy to reverse immune suppression in breast cancer and advance precision immunotherapy.

We also identified dHTC3, a molecular glue that selectively dimerizes BRD4 bromodomain 1 to SCFFBXO3, an E3 ligase not previously accessible for chemical rewiring. Altogether, this study introduces HTC as a facile tool to discover new CIPs and new effectors for proximity pharmacology.

The results demonstrated that GNE-987 significantly enhances the activity of the HCP5 Super-enhancer and inhibits T-ALL cell proliferation while promoting apoptosis by downregulating BRD4. This study suggests that BRD4 and HCP5 are potential therapeutic targets for T-ALL, and GNE-987 provides a novel therapeutic strategy by targeting this regulatory axis, laying the foundation for precision therapy in T-ALL.

Therapeutically, combined treatment with the BRD4 inhibitor JQ1 or the first bromodomain (BD1) selective inhibitor MS402 and an anti-GM-CSF antibody markedly suppressed TNBC progression and converted the tumor immune microenvironment from "cold" to "hot". In conclusion, our study reveals a previously unrecognized metabolic-epigenetic mechanism through which BRD4 drives GM-CSF-dependent TAMs activation and immune evasion in TNBC. Targeting BRD4 in combination with GM-CSF blockade represents a promising therapeutic strategy to overcome immune resistance in this aggressive breast cancer subtype.

Furthermore, CR10 significantly inhibited the growth of MV4-11 and A549 xenograft tumors at a dose as low as 2 mg/kg, without apparent toxicity. This semi-rigid linker-containing degrader represented a promising new mechanism-based candidate for the treatment of hematologic malignancies and lung cancer, warranting further investigation.

In this study, we hypothesize that SB-216 and Veru-111 (related novel compounds) inhibit cell growth via suppression of oncogenic βIII- and βIVb-tubulin subtypes and mitochondria function via suppression of BRD4, the most active BET protein...Our data demonstrates that SB-216 effectively inhibits PDAC cell growth through inhibiting oncogenic microtubules and mitochondrial function. This novel approach simultaneously targets two hallmarks of cancer and patient demise.

The present reactive oxygen species responsive delivery of cytotoxin doxorubicin via a click-to-release reaction between boronate-caged dihydrotetrazines and trans-cyclooctene modified doxorubicin shows excellent chemotherapeutic efficacy and safety in suppressing the growth of some tumors, superior to both direct administration of doxorubicin and reactive oxygen species sensitive prodrug of boronate-caged doxorubicin. We expect this reactive oxygen species responsive bioorthogonal reaction will offer compelling opportunities for precision therapy and provide approaches for studying pathogenesis.

Furthermore, MBD3 is transcriptionally regulated by bromodomain-containing protein 4 (BRD4), and MBD3 knockdown enhances the sensitivity of CRPC cells to BET inhibitors. These findings suggest that the BRD4-MBD3-PTEN axis is a new pathway in CRPC, with MBD3 representing a potential therapeutic target, particularly in combination with BET inhibitors.