JQ-1 / Roche - LARVOL DELTA

Large-scale organoid-derived cyst cultures as a drug discovery platform for polycystic kidney disease. (PubMed, Kidney Int) - "We have developed a scalable method to generate cystic UB organoids, providing a simple and efficient platform for ADPKD drug discovery."

IO biomarker • Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • TLR4

Targeted BRD4 degradation by multivalent dendrimer-based PROTAC and its combined effects with chemotherapy on colon cancer. (PubMed, Biomaterials) - "This study introduces a dendrimer-based proteolysis-targeting chimera (PROTAC) system, JTP, generated by conjugation of polyamidoamine (PAMAM-G4) dendrimer with 4-hydroxythalidomide (an E3 ligase recruiter) and JQ1 carboxylic acid (a BRD4 inhibitor)...In vitro, JTP effectively increased the chemosensitivity of CT26 colon cancer cells to chemotherapy, particularly to irinotecan, leading to enhanced DNA damage, cell cycle arrest in the S and G2/M phases, and apoptosis, as well as a synergistic reduction in oncoprotein expression...The in vivo studies also demonstrated the robust effects of JTP on reducing the expression of TFEB, c-Myc, β-catenin, Bcl-2, VEGFR2, IL-1β, TNF-α, HIF-1α, and vimentin by BRD4 elimination in tumor tissues. These findings demonstrate that combining JTP with epigenetic modulation offers an effective strategy to promote chemotherapeutic effects in colon cancer."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • BCL2 • BRD4 • CTNNB1 • HIF1A • IL1B • KDR • MYC • TFEB • TNFA • VIM

Preclinical evaluation of JQ1 in esophageal squamous cell carcinoma: growth and migration suppression with BRD4-associated DNA damage and apoptotic signaling. (PubMed, Front Pharmacol) - "These effects were accompanied by BRD4-related signaling changes, DNA damage-associated responses, and apoptosis-related molecular alterations. The findings support further investigation of BET/BRD4-associated pharmacological strategies in ESCC, while target-specific validation and expanded in vivo mechanistic and safety studies remain warranted."

IO biomarker • Journal • Preclinical • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • BAX • BCL2 • BRD4 • CASP3 • CCND1 • MYC

Novel far-red fluorescent theranostic probes for selective imaging and targeted therapy of BET proteins in breast cancer. (PubMed, Eur J Med Chem) - "Significantly, L3 facilitated selective imaging of BRD2/3/4 proteins with a clear distinction between malignant and healthy tissues, while also displaying potent in vitro anticancer activity comparable to JQ1(+), by regulating cell cycle- and apoptosis-associated genes. Furthermore, in vivo imaging studies confirmed the potential of this agent for fluorescence-directed tumor excision surgery. Such results position L3 as a multifunctional chemical tool that integrates real-time visualization with therapeutic efficacy for application in breast cancer investigation."

Journal • Breast Cancer • Oncology • Solid Tumor • BRD2

Identification of novel diimide and hydrazone scaffolds for synergistic HIV-1 shock and kill strategies. (PubMed, Biochem Biophys Res Commun) - "RNA-sequencing analyses indicated that compound #C4, JQ1 and PKC activators mediated LRA activity through distinct molecular mechanisms. Collectively, these findings delineate a structurally novel class of LRA candidates that engage a latency-reversal mechanism distinct from that of JQ1 and canonical PKC signaling, and thereby support further investigation of their utility within combinatorial strategies aimed at HIV-1 reservoirs."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

BRD4 Inhibition Mitigates Acute and Chronic Corneal Injury Following Topical Nitrogen Mustard Exposure. (PubMed, Mol Ther) - "Short-term topical BRD4 inhibition with JQ1 reduced acute corneal inflammation (e.g., reducing CD45+ cells by 86%) and oxidative stress, and conferred long-term preservation of corneal clarity, stromal organization, and endothelial integrity...Mechanistically, BRD4 inhibition selectively counteracted key NM-driven pathogenic programs, including inflammation, oxidative stress, and extracellular matrix remodeling. These findings identify BRD4 as a central epigenetic driver of vesicant-induced corneal injury and position BRD4 inhibition as a promising translational therapeutic strategy."

Journal • Corneal Abrasion • Inflammation • Keratitis • Ocular Inflammation • BRD4 • PTPRC

Phase separation of ecDNA condensates establishes in-trans contact domains that boost selective MYC regulatory interactions. (PubMed, Nat Commun) - "The BET inhibitor JQ1 reverses ecDNA phase separation, abolishing I-TADs and reducing MYC transcription in a switch-like manner, as confirmed by RT-qPCR experiments. These findings clarify the role of ecDNA condensates in gene regulation and highlight potential therapeutic strategies targeting BRD4-mediated interactions."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BRD4 • PVT1

Biomimetic hybrid nanoparticles from grape-derived exosome-like particles and liposomes potentiate JQ1-mediated anti-fibrotic effects in hepatic stellate cells. (PubMed, J Pharm Sci) - "These findings indicate that GELP-liposome hybridization is an effective strategy for JQ1 delivery and that Hybrid@JQ1 alleviates fibrotic phenotypes in activated HSCs in vitro. Our study provides a promising plant-derived biomimetic nanoplatform for anti-fibrotic drug delivery."

Journal • Fibrosis • Immunology • Inflammation • Liver Cirrhosis • COL1A1 • COL3A1 • IL6 • NOX4 • TGFB1 • TNFA

Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4-Dependent Enhancer Activation. (PubMed, Adv Sci (Weinh)) - "In an orthotopic mouse model, BRD4 inhibition using JQ1 or MZ1 suppresses 4T1 cell metastasis...BRD4 and EDN1 expression is commonly upregulated in human breast metastasis. These findings define nutrient stress-responsive enhancers as epigenetic drivers of metastatic adaptation and highlight their therapeutic potential in breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • ATF3 • BRD4 • EDN1 • JUN

High-throughput synthesis and anticancer evaluation of novel benzo[f]tetrazolo[1,5-a][1,4]diazepines via a one-step multicomponent reaction | Poster Board #1491 (ACS-Fall 2026) - "Several derivatives exhibited sub-micromolar potency, demonstrating superior anti-proliferative activity compared to the gold-standard BET inhibitor, JQ1. This enhanced potency is attributed to the synergistic integration of the benzodiazepine scaffold with a tetrazole bioisostere, which optimizes molecular interactions and improves metabolic stability. This work establishes the tetrazolo-fused benzodiazepine framework as a high-value scaffold and provides an efficient methodology for the rapid expansion of the anticancer chemical space."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Insomnia • Mood Disorders • Oncology • Sleep Disorder

Discovery of selective and potent BCL6 transcriptional chemical inducers of proximity through linker optimization (ACS-Fall 2026) - "A library of 66 heterobifunctional analogs based on JQ1 (BRD4 inhibitor) and BI-3812 (BCL6 inhibitor) was synthesized and evaluated for ternary complex formation, as well as cellular activity and selectivity across several cell lines. Computational analysis suggested that conformationally constrained linkers reduce the entropic penalty associated with ternary complex formation. These results show that the linker nature is an important factor of TCIP performance and also support transcriptional chemical induction as a viable strategy for targeting BCL6."

BCL6 • BRD4

An optimized RNF126-targeting covalent handle for molecular glue degraders. (PubMed, Bioorg Med Chem Lett) - "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

A BRD4/p300/SP1 epigenetic cascade drives microglial P2X4R transcription and promotes neuropathic pain. (PubMed, J Neuroinflammation) - "Disruption of this cascade via p300 inhibition (C646) or BRD4 blockade (JQ1) attenuated spinal neuroinflammation and alleviated nociceptive hypersensitivity. Notably, reactivation of P2X4R by BzATP largely reversed the analgesic effects of BRD4 inhibition, establishing P2X4R as a critical downstream effector. Collectively, these findings support a p300-BRD4-SP1 epigenetic cascade linking chromatin remodeling to microglia-mediated neuropathic pain, highlighting this pathway as a potential therapeutic target."

Journal • Immunology • Inflammation • Neuralgia • Pain • BRD4 • P2RX4

Metabolite sensing in cardiometabolic HFpEF: mechanisms and therapeutic perspectives. (PubMed, Diabetes Res Clin Pract) - "Therapeutically, while SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone provide clinical benefits by restoring metabolic-cardiac homeostasis, targeting upstream metabolite-sensing pathways, such as epigenetic modifier regulators JQ1 and RVX-208 and gut microbiota metabolites, shows great potential. Ultimately, understanding how metabolites are sensed and translated into pathological signals is a key breakthrough for achieving precision therapy in cardiometabolic HFpEF."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Genetic Disorders • Heart Failure • Immunology • Inflammation • Metabolic Disorders • Obesity

BET inhibition unmasks a targetable glycolytic dependency through a HIF1α stabilization and driven transcriptional program in a defined subset of triple-negative breast Cancer. (PubMed, Cell Death Discov) - "Here, we investigated the responses to the BETi JQ1 and OTX015 across a heterogeneous panel of TNBC models...While the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) is effective as a single agent in the glycolytic-prone setting, it has limited efficacy in other TNBC models...By mapping a transcriptional-metabolic axis that dictates BETi sensitivity, this study moves beyond the identification of a resistant subset of TNBC to reveal a deeper principle: targeted inhibition can actively reprogram cellular circuitry, thereby constructing its own unique therapeutic vulnerability. Thus, the path to overcoming resistance may lie not in evading this rewiring, but in strategically exploiting the alternative dependencies it creates."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRD4 • HIF1A • MYC

BET inhibition synergizes with RLR signaling to enhance tumor immunogenicity and T cell recognition. (PubMed, Cancer Immunol Res) - "Furthermore, an antiviral gene signature induced by poly(I:C) and enhanced by JQ1 correlated with immune infiltration and improved survival in larger patient cohorts across different types of cancer. Overall, our findings demonstrate that targeting BET proteins in tumor cells strongly potentiates dsRNA-induced antiviral responses and suggests that combining BET inhibitors with RLR agonists offers a pharmacological strategy to enhance antitumor T cells responses and improve the clinical efficacy of cancer immunotherapies."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • CD8 • IFIH1

A Pancreatitis-Inspired Trypsinogen Nanoplatform Reprograms Tumor-Associated Macrophages via NF-κB for Pancreatic Cancer Immunotherapy. (PubMed, Adv Sci (Weinh)) - "To harness this activity, a pancreatitis-inspired nanoplatform (JT@NPs-aCD11b) co-delivering trypsinogen and the CD47 inhibitor JQ1 to TAMs is developed...Macrophage depletion abrogated efficacy, confirming TAMs as the primary mediators. This work establishes trypsinogen as a versatile immunomodulator and its nanoplatform as a promising strategy for pancreatic cancer immunotherapy."

Journal • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • PRSS1

Cell-Penetrating Peptide Conjugated Polyzwitterion-Drug Enhances Tumor Retention. (PubMed, Nano Lett) - "Consequently, the optimized TAT12-PEG-SN38 micelles prolonged blood circulation and suppressed TNBC growth and metastasis. Furthermore, combination treatment with JQ-1 attenuated immune evasion. Overall, peptide structure engineering overcomes the PEG barrier, providing a practical strategy for developing novel peptide-drug conjugates."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Design of Potent and Selective BCL6 Transcriptional Chemical Inducers of Proximity through Linker Optimization. (PubMed, J Med Chem) - "A focused library of 66 heterobifunctional analogues derived from JQ1 and BI-3812 was evaluated for ternary complex formation, cellular potency, and selectivity. Computational analyses, competition experiments, and RNA sequencing indicate that the effects of the optimized analogues are driven by ternary complex formation. Together, these findings establish the linker architecture as a critical determinant of TCIP performance."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • BCL6

JQ1 Downregulates IL-20RA Expression in Triple Negative Breast Cancer Cells In Vitro and In Vivo. (PubMed, Int J Mol Sci) - "Parallel in vivo experiments using TNBC xenograft models confirmed these findings, showing reduced IL-20RA and PD-L1 expression alongside decreased phosphorylation of JAK and STAT3. Overall, this study uncovers a novel interplay between BET inhibition and the IL-20RA/STAT3 axis, suggesting JQ1 as a valid therapeutic option for TNBC characterized by high IL-20RA expression."

IO biomarker • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

scTumorDrug: predicting cell-type-specific drug responses for heterogeneous tumors. (PubMed, Brief Bioinform) - "This observation also provided an explanation for JQ1 efficacy. To summarize, the scTumorDrug can be used in broad application scenarios and we provided cell-type-specific drug response prediction and validation."

Heterogeneity • Journal • Bladder Cancer • Oncology • Solid Tumor

Super Enhancers Regulate Growth and Viability of Cutaneous Squamous Carcinoma Cells (EACR 2026) - "Super enhancers (SE) are known to induce the transcription of oncogenes and promote cancer.Material and We study patient-derived cSCC cells and the role of SE in progression of cSCC using two small molecule inhibitors targeted to SE-related cofactors BRD4 and CDK7 (JQ1 as BRD4i, THZ1 as CDK7i)... SE cofactors BRD4 and CDK7 could serve as therapeutic targets in locally advanced and metastatic cSCC."

Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • BRD4 • CDK7 • MAPK13 • MAPK3 • MMP1

Mechanisms of Resistance and Novel Therapeutic Strategies to Overcome BET Inhibitor Resistance in Pediatric Fusion-Positive Rhabdomyosarcoma (EACR 2026) - "Pharmacological inhibition of BET proteins with JQ1 disrupts P3F and BRD4 interaction, halting tumor growth. These findings suggest that activation of the MEK/ERK pathway could drive resistance to BET inhibition through MYCN stabilization. Combined MEK/ERK and BET inhibition may potentially represent a promising therapeutic strategy for both resistant and sensitive FP-RMS."

Clinical • Colon Cancer • Colorectal Cancer • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ANXA5 • BRD4 • MYCN • PAX3

Co-Delivery of Chemo and Immune Drugs by Prussian Blue Nanocubes for Combinational Therapy and T1-T2W MR Imaging of MDA-MB-231. (PubMed, ACS Appl Bio Mater) - "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."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • IL1B • PD-L1

PROTEIN KINASE CK2 AS A THERAPEUTIC HUB IN MANTLE CELL LYMPHOMA: FROM INFLAMMATION TO DRUG RESISTANCE (EHA 2026) - "Methods MCL cell lines were treated with CK2 inhibitors (CX-4945, SGC-CK2-1) or subjected to CK2 gene silencing alone and in combination with BETi (JQ-1, INCB054329). Summary/Conclusion These /ndings identify CK2 as a key driver of oncogenic transcription, infiammatory signaling, and adaptive resistance in MCL. CK2 inhibition disrupts tumor-promoting cytokine networks and restores sensitivity to BET inhibitors, supporting combination strategies aimed at enhancing therapeutic efficacy and overcoming drug resistance."

IO biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • BCL2 • BRD4 • CCL18 • CXCR4 • IFNG • IL10 • MYC • TGFB1 • TNFA