JQ-1 / Roche - LARVOL DELTA

A photothermal immune hydrogel dressing for enhanced post-melanoma resection treatment. (PubMed, J Nanobiotechnology) - "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."

IO biomarker • Journal • Infectious Disease • Melanoma • Oncology • Solid Tumor • BRD4 • IFNG • PD-L1

High-intensity interval training alleviates COPD-induced gastrocnemius muscle dysfunction via the BRD4/PGC-1α axis through restoring mitochondrial function and oxidative fiber composition. (PubMed, J Muscle Res Cell Motil) - "HIIT significantly improved pulmonary function, muscle strength, and oxidative fiber composition in COPD rats by restoring the BRD4/PGC-1α axis and mitochondrial function, but the BET bromodomain inhibitor JQ1 could partially reverse the positive effects of HIIT. These findings not only provides some scientific evidence for the beneficial effects of HIIT on gastrocnemius muscle dysfunction caused by COPD but also suggest that the BRD4/PGC-1α axis plays functional roles in mediating the beneficial effects of HIIT on COPD-induced muscle dysfunction, highlighting its potential as a therapeutic target. The online version contains supplementary material available at 10.1007/s10974-026-09723-4."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Muscular Atrophy • Pulmonary Disease • Respiratory Diseases • BRD4

An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders. (PubMed, bioRxiv) - "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."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • Transplantation • BRD4

Construction and evaluation of a bladder cancer prognosis model based on super-enhancer-associated genes. (PubMed, Discov Oncol) - "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."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4 • CD8 • KRAS • MXRA7

TDP-FM: A MULTIMODAL FOUNDATION MODEL FOR TDP-43 PROTEINOPATHIES AND THERAPEUTIC TARGET DISCOVERY (ADPD 2026) - "In silico screening of >300 compounds identified JQ1-BET inhibitor as top candidate for ALS... TDP-FM is a framework for generalizable TDP-43 research and therapeutic discovery that couples EHR-derived features with TDP-43–centric molecular representations and insilico drug screening. The same can be applied to FTLD, LATE, AD, PD to identify shared and disease-specific therapeutic targets across the proteinopathy spectrum and create a mechanistic TDP-43 network atlas."

Frontotemporal Lobar Degeneration • Proteinopathy • STMN2 • TARDBP

Characterization of TKI-induced drug-tolerant persister cells from patient-derived cell lines (AACR 2026) - "The two main models used were MR57, harboring EML4-ALK fusion and ALK C1156Y/G1269A mutation and sensitive to the 3rd generation ALK inhibitor lorlatinib, and ST6566, carrying an EGFR L858R mutation and highly sensitive to osimertinib.Results and DTP cells are characterized by marked phenotypic plasticity...These experiments revealed that targeting EMT-associated transcriptional control with the BRD4 inhibitor JQ1, inhibiting FGFR-driven signaling with erdafitinib, or blocking DNA-damage repair via the ATM inhibitor AZD-0156 each significantly delayed DTP regrowth. Overall, our results demonstrate that DTP cells regrowth can be delayed in vitro, suggesting exploitable vulnerabilities. While further validation is required, they provide a rational for testing these strategies in vivo, with an ultimate goal of informing patient therapeutic approach."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRD4 • EGFR • EML4 • STING

BET domain functions in IDH1R132H/p53mut/ATRXloss astrocytoma malignancy (AACR 2026) - "Consistently, the immunoblot analysis showed that BRD3 expression is induced by the triple-mut and further enhanced by ionizing radiation (IR) and temozolomide (TMZ) treatment. Functionally, inhibition of BET proteins using either pan-BET inhibitors (JQ1, OTX015) or bromodomain 1 (BD1)-selective inhibitor GSK778—but not bromodomain 2 (BD2)-selective inhibitor GSK620— markedly reduces triple-mut glioma cell growth and impairs neurosphere self-renewal, and enhances TMZ-induced cell death...These findings identify a BD1-dependent transcriptional network that regulates astrocytoma cell phenotype and contributes to an immunosuppressive microenvironment. Targeting BD1 represents a rational therapeutic strategy by simultaneously suppressing tumor cell-intrinsic oncogenic signaling (e.g.,YAP1/TAZ signaling) and reshaping the immunosuppressive microenvironment."

IO biomarker • P53mut • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • BRD2 • BRD3 • IDH1 • IFNG • TAFAZZIN • YAP1

The IKZF1 N159Y partial tandem duplication mutant drives chromatin remodeling, B-cell developmental defects and leukemia initiation (AACR 2026) - "N159Y leukemia cells showed dependency on EP300 and CREBBP, and sensitivity to A-485, JQ1, and vorinostat. We show that N159Y is a chromatin-remodeling transcription factor mutant with neomorphic chromatin-binding. It disrupts B cell development and induces B-ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CREBBP • EP300 • IKZF1 • MCL1

BRD- and EHMT-dependent immunosuppressive transcriptome in triple-mutant Astrocytoma (AACR 2026) - "Furthermore, we found that the components of the immune-modulating transcriptome associated with triple-mut astrocytom are augmented by standard-of-care radiation (IR) and temozolomide (TMZ). Pan-BET bromodomain inhibitors (e.g., JQ1) significantly inhibited the immunosuppressive transcriptome associated with triple-mut astrocytoma and induced by IR/TMZ, and the pan -EHMT inhibitor UNC0642 significantly up-regulated MHC APP genes and IFN signaling-related genes. SIGNIFICANCE: our findings identify targetable epigenetic determinants that induce an immunosuppressive transcriptome associated with the immunosuppressive microenvironment in triple-mut astrocytoma."

Astrocytoma • Brain Cancer • Oncology • Solid Tumor • ATRX • IFNG • TP53

The SOX2-RUNX2/TEAD4 signaling axis drives ESCC progression and exposes therapeutic vulnerabilities via Hippo/MAPK pathways (AACR 2026) - "Therefore, we evaluated the therapeutic efficacy of the MEK inhibitor trametinib, the TEAD4 inhibitor IAG933, and the BRD4 inhibitor JQ1 using both organoid and cell line models. In conclusion, our study uncovers a novel epigenetic mechanism driving SOX2-amplified ESCC and identifies the SOX2-RUNX2/TEAD4 axis as a promising therapeutic target. These findings provide a strong preclinical rationale for evaluating therapeutic strategies targeting this axis in clinical trials for patients with this aggressive malignancy."

Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • BRD4 • CCN1 • CDKN2A • CTGF • RUNX2 • SOX2 • TEAD4 • TP53 • YAP1

Chemical Space Navigation of Nitidine Leads to the Discovery of a Novel PD-L1 Degradation Agent by Targeting CSN5 for Enhanced Antitumor Immunity. (PubMed, J Med Chem) - "Activity screening identified derivative e24, which reduced tumor cell PD-L1 expression more effectively than positive control JQ-1, while the prototype nitidine had minimal effects. Critically, e24 specifically targets CSN5, an essential regulatory factor, to induce PD-L1 degradation, thereby blocking the PD-1/PD-L1 interaction between T cells and tumor cells and activating the tumor immune microenvironment. In Lewis tumor and MC38 mice models, e24 exerted antitumor effects by enhancing tumor-infiltrating T-cell immunity and inhibiting the activation of immunosuppressive MDSCs and Tregs."

IO biomarker • Journal • Oncology • PD-L1

BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response. (PubMed, NPJ Precis Oncol) - "BET inhibition with (+)-JQ1 diminished FOXM1/MYC promoter occupancy at BRCA1 and RAD51, downregulated HR genes, and synergized with PARPi in viability and clonogenic assays. A BRD4 degrader (ZBC260) achieved potent BRD4 depletion at low nanomolar doses, suppressed FOXM1/MYC and HR gene expression, enhanced PARP1 trapping, and produced strong synergy with olaparib, including in patient-derived cancer cells. Clinically, BRD4 is highly expressed in ovarian cancer and independently predicts poor survival, outperforming FOXM1 and MYC. These data establish BRD4-directed disruption of the FOXM1-MYC axis as a strategy to induce "BRCAness" and broaden PARPi efficacy."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • BRD4 • FOXM1 • MYC • RAD51

Accessibility at a primed distal Fshb-Kcna4 super-enhancer is facilitated by Foxl2 during gonadotrope differentiation. (PubMed, Endocrinology) - "Expression of Fshb and Kcna4 was strongly inhibited by JQ-1, which represses super-enhancer activity, and the region displays super-enhancer characteristics...Foxl2 was found to bind this element, contributes to maintaining its chromatin accessibility, and recruits Supt16h, a component of the Facilitates Active Chromatin Transcription (FACT) histone chaperone complex. These findings define a distal, Foxl2-bound super-enhancer that regulates Fshb transcription and shapes the gonadotrope regulatory landscape."

Journal • BRD4 • FOXL2 • FSHB • MBD4 • MED1

Superenhancer-mediated ferroptosis in age-related hearing loss: cochlear epigenomics. (PubMed, Cell Mol Life Sci) - "This study provides evidence for the role of Sp1 and Fth1 in the regulation of HC aging and ARHL. These findings suggest that manipulating SE sites and inhibiting ferroptosis may offer novel therapeutic strategies for treating ARHL. Understanding the interplay between SEs, Sp1, Fth1 and ferroptosis reveals novel targets for AAV gene therapy to preserve hearing in aging populations by modulating iron homeostasis during sensory cell senescence."

Journal • Gene Therapies • Hematological Disorders • Otorhinolaryngology • FTH1

MYC-Mediated Functional Manifestation of IDH1 Mutations in Intrahepatic Cholangiocarcinoma Confers Sensitivity to (+)-JQ1. (PubMed, Int J Biol Sci) - "Notably, ICC with concurrent IDH1 mutations and MYC amplification exhibited sensitivity to the MYC inhibitor (+)-JQ1, but remained resistant to the IDH1 mutation inhibitor AG120. MYC overexpression conferred resistance to IDH1 mutation inhibitor, while creating a therapeutic vulnerability to MYC-targeted agents. The selective efficacy of (+)-JQ1 against IDH1-mutant ICC identified MYC inhibition as a promising precision medicine strategy for this molecular subset."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1 • KRAS • MYC • TP53

BET inhibition enhances temozolomide sensitivity in cervical cancer cells through ALDH suppression and epigenetic reprogramming. (PubMed, Mol Biol Rep) - "This study demonstrates that BET inhibition by JQ1 influences cellular sensitivity to TMZ and is associated with altered oxidative stress parameters and transcriptional reprogramming of epigenetic regulators in cervical cancer cells. While further protein-level and functional validation is required to establish causal mechanisms, these findings support the potential of BET-targeted strategies to modulate therapeutic responses in cervical cancer."

Journal • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • ALDH1A1 • ANXA5

(+)-JQ1 Upregulates SIRT3 to Suppress cGAS/STING Pathway-Mediated Neuronal Inflammation and Ferroptosis After Hypoxic-Ischemic Encephalopathy. (PubMed, Drug Des Devel Ther) - "JQ1 exerts neuroprotective effects in neonatal hypoxic-ischemic encephalopathy by attenuating neuroinflammation and suppressing ferroptosis. We demonstrate that SIRT3 upregulation in the brain underlies the neuroprotective role of JQ1."

Journal • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • GPX4 • SIRT3

BRD4 orchestrates the metabolic-epigenetic regulation of GM-CSF expression and secretion to drive PD-L1⁺ macrophage-mediated immune evasion in triple-negative breast cancer. (PubMed, Oncogene) - "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."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRD4 • CSF2 • PD-L1 • PKM

SHP2 improved Late-onset fetal growth restriction via modulating ROS/BRD4/PI3K/YAP/PIGF signaling induced angiogenesis. (PubMed, PLoS One) - "SHP2 improves LO-FGR by regulating ROS/BRD4 and PI3K/YAP/PIGF-induced activation of endothelial progenitor cells."

Journal • BRD4 • HIF1A • MYC • NOX4 • POU5F1 • SOX2

ROLE OF CHROMATIN MODIFICATIONS IN NEONATAL ATTENUATED HEPATOCYTE INNATE IMMUNE RESPONSE (WRMC 2026) - "To assess whether histone acetylation influences transcription of cytokine-induced innate immune genes, adult hepatocytes were exposed to IL-1β/IL-6 ± JQ1 (5μM, 24h)... P3 hepatocytes exhibited attenuated transcriptional responses to proinflammatory stimuli across several p-STAT and C/EBPβ targets, a finding replicated in adult hepatocytes with disruption of histone acetylation. Genome-wide analyses are needed to better define neonatal chromatin accessibility, which may provide critical insights for developing strategies to prevent neonatal sepsis."

Infectious Disease • Inflammation • Septic Shock • CXCL1 • CXCL10 • IL1B • IL6 • IRF1 • NFKBIA • SAA1 • SOCS3 • SOD2

A Spatiotemporally Controlled Nanoplatform for Photothermal BRD4 Degradation Enables Synergistic Cancer Immunotherapy. (PubMed, Adv Sci (Weinh)) - "We constructed a multifunctional theranostic nanoplatform (PCN-CuS-JQ/RGD) based on an MRI-visible, Fe-porphyrin MOF (PCN(Fe)) carrier, decorated with CuS photothermal agents, a BRD4 inhibitor (JQ1), and a tumor-targeting peptide (RGD)...Crucially, in a bilateral tumor-bearing mouse model, our strategy demonstrated a powerful synergistic effect, significantly enhancing the efficacy of anti-PD-L1 immune checkpoint blockade therapy. This work presents a light-activatable degradation platform that achieves high tumor selectivity and potent immunotherapy, offering a promising new avenue for cancer treatment."

IO biomarker • Journal • Oncology • Targeted Protein Degradation • BRD4

Unraveling AMPK and BET regulation of immune checkpoint biology: implications for personalized medicine. (PubMed, bioRxiv) - "Immune suppression in T2D, and use of metformin, an activator of 5' Adenosine Monophosphate-activated Protein Kinase (AMPK), in such patients, prompted us to examine AMPK regulation of immune checkpoint expression. Chemical inhibition of AMPK with Compound C, and with the pan-BET inhibitor JQ1 or the BRD4-selective PROTAC inhibitor MZ-1, revealed that BET proteins regulate PD-1 and CTLA-4 through an AMPK-dependent pathway and TIM-3 and TIGIT through an AMPK-independent pathway. Personalized approaches to ICB treatment of TNBC patients with comorbid T2D should improve outcomes."

IO biomarker • Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • Type 2 Diabetes Mellitus • AMPK • BRD2 • BRD3 • BRD4 • CD4 • CD8 • TIGIT

Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580. (PubMed, PLoS Pathog) - "We previously identified ZL0580, a first-in-class BRD4-selective small molecule distinct from the pan-BET inhibitor JQ1, which induces HIV epigenetic suppression...In a humanized mouse model of HIV infection, ZL0580 monotherapy, or in combination with ART, potently suppressed active HIV replication, reducing the plasma viremia to nearly undetectable levels, and delayed viral rebound following treatment interruption. Collectively, these findings establish ZL0580 as an epigenetic suppressor of HIV in vivo and provide proof-of-concept for its potential as a "block and lock" HIV cure candidate, warranting further optimization and development."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • BRD4

Discovery of SKP2-Recruiting PROTACs for Target Protein Degradation. (PubMed, Adv Sci (Weinh)) - "We designed and synthesized SKP2-recruiting degraders by linking SL1 to the BRD4 inhibitor JQ1...We further demonstrate that SKP2-directed PROTACs effectively degrade Androgen receptor (AR) in 22RV1 cells. These findings emphasize that SKP2, frequently overexpressed in various tumor cells, can be successfully exploited for TPD through non-covalent PROTACs, expanding the pool of E3 ligases available for potential therapeutic applications."

Journal • Oncology • Targeted Protein Degradation • AR • BRD4 • SKP2

HB023: A glutamine antagonist prodrug boosting antitumor lmmunity via PD-L1 suppression and mitochondrial membrane remodeling. (PubMed, J Adv Res) - "HB023 successfully addresses the challenge of glutamine deprivation-induced immune escape by integrating metabolic inhibition with immune checkpoint blockade. This dual-modulatory approach reprograms the tumor immune microenvironment and improves immunotherapeutic efficacy, representing a promising strategy for advancing cancer treatment."

IO biomarker • Journal • Oncology • PD-L1