JQ-1 / Roche - LARVOL DELTA

Activation effects of chidamide on BET signaling pathways and the mechanism of synergistic effect with BET inhibitors in Mantle Cell Lymphoma (ASH 2025) - "The cytotoxic effects of varying doses (0–20 μM) of the BET inhibitor JQ1 on the mantle cell lymphoma cell line (Maver-1) were assessed, and its half-maximal inhibitory concentration (IC50) was determined. This study represents the first exploration of dual epigenetic therapy in MCL. Our goal is to elucidate the mechanisms by which chidamide exerts its therapeutic effects in MCL through regulation of the BET signaling pathway, ultimately providing a theoretical foundation for dual epigenetic therapy in B-cell lymphoma."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Gene Therapies • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • HDAC1 • HDAC2 • HDAC6

Targeting BRD4 to reshape the inflammatory microenvironment of senescent bone marrow mesenchymal stem cells for improved hematopoietic stem cell transplantation reconstitution (ASH 2025) - "Crucially,dual-pathway intervention combining senolytic agents (dasatinib + quercetin, D+Q) with JQ1 exhibitedsynergistic efficacy, reducing SASP secretion more substantially than either monotherapy...We further demonstrate that a novel dual-pathway strategy combiningsenescent cell clearance (via dasatinib + quercetin) with BRD4 inhibition synergistically restores theinflammatory hematopoietic microenvironment. This approach offers a promising therapeutic solutionfor improving post-transplantation HSC reconstitution, with BRD4-targeted interventions demonstratingsignificant potential for clinical translation."

Bone Marrow Transplantation • Transplantation • BRD4

Allele-dependent activity of promoters of genes SLC22A4 and SLC22A5 encoding imatinib transporters in chronic myeloid leukemia (ASH 2025) - "Regardless of the allele, promoter activity decreasedafter JQ1 treatment (MYC expression inhibitor), confirming the rs460089 as a biologically relevant MYCbinding site as predicted by previous in silico analysis. Our results revealed that the rs460089 locus, which is in strong linkage disequilibrium withregulatory elements in the SLC22A5 promoter, exerts a significant allele-specific effect on promoteractivity, leading to altered SLC22A5 transcription and accumulation of intracellular carnitine. Elevatedcarnitine concentrations (potentially supported by ergothioneine antioxidant activity) may enhance thesurvival of CML cells. Modulated carnitine-dependent metabolic pathways may potentially explain thepreviously observed association between rs460089 and both imatinib response and treatment-freeremission (TFR) in CML."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • MYC

Super-enhancer-mediated regulation of CD38 inducibility in multiple myeloma via the MAF/TRIM47/RARα axis (ASH 2025) - "Functional validation using the SE inhibitor JQ1 and sgRNA-mediated targeted deletion confirmed four critical SE sites; disruption of these sites markedly diminishedboth MAF/H3K27ac enrichment and TRIM47 expression...Importantly, these results suggestthat patients with t(14; 16) or other high-MAF-expressing MM subtypes may exhibit diminishedresponsiveness to ATRA-mediated enhancement of CD38-targeted immunotherapy efficacy due toTRIM47-dependent RARα degradation. Targeting this axis represents a potential therapeutic strategy forthis adverse-risk patient group."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • IFNG • MAF • RARA • TNFA • TRIM47

Neomorphic chromatin engagement and epigenetic reprogramming by the IKZF1 N159Y tandem duplication mutant in b-acute lymphoblastic leukemia (ASH 2025) - "Cytotoxicity assays were used to assess sensitivity to 3 epigenetic modulatorsincluding inhibitors of histone acetylation (A-485 and JQ1) or deacetylation (vorinostat). Cooperative binding with WT IKZF1 and binding at de novosites, not bound by WT, suggest partial dominant and neomorphic functions of the TD mutant. Ourfindings define a distinct chromatin regulatory program in IKZF1 N159Y leukemia and suggesttherapeutic vulnerability to epigenetic modulators targeting histone acetylation."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • ABL1 • DUX4 • EP300 • IKZF1 • MCL1 • TGFB1

Combined Inhibition of Protein Kinase CSNK2 and BET Proteins As a Novel Therapeutic Strategy for Mantle Cell Lymphoma (ASH 2023) - "Currently available therapeutic approaches for Mantle Cell Lymphoma (MCL), including the Bruton Tyrosine Kinase (BTK) inhibitors ibrutinib, acalabrutinib and zanubrutinib, are not curative...In MCL, BET inhibitors, such as INCB054329 or JQ-1, have been shown to increase apoptosis through downregulation of the AKT-mTOR, ERK, and other B Cell Receptor (BCR)-triggered cascades...The most effective and tested CSNK2 chemical inhibitor is CX4945 (silmitasertib), but very recently a novel compound, SGC-CK2, has been developed...Remarkably, CK2 inactivation led to a robust reduction of the BET inhibitor-induced increase of Mcl1, and NF-kB Ser 529 phosphorylation, thus counteracting BET-inhibitors-evoked compensatory pathways that could favor apoptosis resistance. Therefore, combined CSNK2 and BET proteins inhibition could represent an innovative strategy for chemotherapy and BTKi-resistant MCL."

Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • ANXA5 • BRD4 • MYC

Actionable Findings from an Unbiased Drug Screen for Novel Single Agent and Combination Therapies Against AML with Mecom Re-Arrangement (ASH 2023) - "This was consistent with previous reports that BET inhibitors (e.g., OTX015, mivebresib or ABBV-075 and JQ1) are effective against 3q26.2-r AML cell lines, patient-derived (PD) AML cells and PDX models...In follow-up experiments, XIAP/cIAPs inhibitors birinapant (10-1000 nM) or SM-164 (30-1000 nM), chosen based on the MIPE screen outcomes, induced significantly more dose-dependent apoptosis in 3q26.2-r versus the other AML cell lines...Treatment with the dual mTOR/PIK3CA inhibitor NVP-BGT226 (1-30 nM) or navitoclax or Bcl-xL-specific BH3 mimetic A-1155463 also exerted lethality and synergistically induced apoptosis with mivebresib in AML cells with inv3/t(3; 3)...Co-treatment with birinapant and tegavivint also synergistically induced apoptosis in 3q26.2-r AML cells...Additionally, compared to each drug or vehicle control, co-treatment with birinapant and the BETi OTX015 (30 mg/kg/day, by oral gavage) was more effective in reducing AML burden in the xenograft model...."

Combination therapy • Acute Myelogenous Leukemia • Oncology • BCL2L1 • BRD4 • CASP3 • CDK4 • CTNNB1 • GATA2 • HEXIM1 • MCL1 • MECOM • MYC • PIK3CA • SF3B1 • XIAP

A Super-Enhancer-Related Ferroptosis Signature Predicts Survival and Immune Microenvironment in Colon Cancer Based on Bioinformatics Analyses and Experimental Validation. (PubMed, IET Syst Biol) - "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."

IO biomarker • Journal • Tumor mutational burden • Colon Cancer • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CAV1 • ENO3 • MSI • TMB

RNA splicing patterns contribute to burst size variation among HIV-1-infected Jurkat cell clones. (PubMed, J Virol) - "This over-splicing clone, which contained a non-synonymous substitution in rev, did not respond to treatment with the latency-reversing agent JQ1 but displayed increased virus release in response to treatment with pladienolide B, a splicing inhibitor...While cell-intrinsic factors appeared to be the primary contributors to heterogeneous shedding patterns, viral point mutations were also observed and, in at least one case, contributed to particle release levels. Together, these findings demonstrate that expression variation among proviruses is both large and multifaceted and suggest that clone-specific differences in HIV-1 expression properties may contribute to unpredicted responses to treatment interventions."

Journal • Human Immunodeficiency Virus • Infectious Disease

Epigenetic profiling reveals key super-enhancer networks driving oncogenesis in HPV-positive HNSCC. (PubMed, iScience) - "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."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRD4 • FOSL1 • TP63

Targeting Mitochondrial Apoptotic Priming State to Personalize Therapy for Relapsed Acute Myeloid Leukemia (ASH 2023) - "We tested in vivo sensitivity to 5 drugs of disparate mechanisms of action: birinapant and LCL-161 (SMAC mimetics), JQ-1 (BRD-4 inhibitor), venetoclax (BCL-2 antagonist), and quizartinib (FLT-3 inhibitor) in 4-9 different PDX models each. Overall, we demonstrate that acquired resistance to targeted therapy in AML is accompanied by common mechanism of reduction in mitochondrial priming along with drug-specific resistance mechanisms. Further, we find that, even in the context of a multiply-resistant PDX model, DBP can still identify therapeutic vulnerabilities that can be efficaciously exploited in vivo."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BRD4 • FLT3 • PTPRC

Hypoxia-activated paclitaxel prodrugs enable PD-L1 degradation to potentiate cancer chemo-immunotherapy. (PubMed, J Nanobiotechnology) - "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."

IO biomarker • Journal • Oncology • PD-L1

Use of Combination Therapies Including the XPO1 Inhibitor Selinexor in Is a Potential Effective Therapeutic Strategy to Treat Myelofibrosis Patients (ASH 2023) - "We also evaluated the ability of SEL alone to eliminate MF CD34+ cells and in combination with other candidate drugs such as HDM201 (HDM2 antagonist), ruxolitinib (RUX), pan-BET inhibitor (JQ1) or a Bcl-2/Bcl-xL inhibitor (navitoclax). The effects of SEL combined with either RUX or an HDM2 antagonist more effectively depleted mutated MF CD34+ cells than either drug alone. The combination of SEL+HDM201 spared the reservoir of WT progenitors, and reduced JAK2 mutated progenitor cells to a great degree suggesting that this combination might be associated with less hematological toxicity and greater efficacy."

Clinical • Combination therapy • IO biomarker • Myelofibrosis • Oncology • BCL2 • BCL2L1 • CCNB1 • CD34 • CDKN1A • MYC • RB1 • TP63 • TP73 • XPO1

Acetylation reader BRD4-driven TXNIP transcription enhances NLRP3 inflammasome activation in PCOS. (PubMed, Cell Mol Life Sci) - "BRD4 and AR exhibited inducible binding to the histone H3 acetylation-enriched TXNIP promoter, whereas intervention with the BRD4-selective inhibitor JQ1 and the AR-selective inhibitor attenuated this binding, leading to subsequent downregulation of TXNIP transcription that ultimately resulted in NLRP3 inflammasome suppression. Our data indicate that BRD4 upregulation and the resultant TXNIP transcriptional activation are crucial regulatory pathways for NLRP3 inflammasome activation, resulting in associated reproductive and metabolic abnormalities in ovarian GCs from PCOS."

Journal • Endocrine Disorders • Infertility • Polycystic Ovary Syndrome • Sexual Disorders • AR • BRD4 • NLRP3 • TXNIP

Retraction Note: Synergy between arsenic trioxide and JQ1 on autophagy in pancreatic cancer. (PubMed, Oncogene) - No abstract available

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Combinational BET and mTOR inhibition unveils EGR1 as acute myeloid leukemia prognostic biomarker. (PubMed, Sci Rep) - "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."

Biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • EGR1

Super-Enhancer-Associated circRHOQ Regulates Intramuscular Fat Deposition by Modulating the miR-5093/IRF5 Axis. (PubMed, J Agric Food Chem) - "Treatment with JQ-1 suppressed circRHOQ expression, confirming that circRHOQ is an SE-driven regulatory circRNA...Dual-luciferase assays validated the direct interactions among circRHOQ, miR-5093, and IRF5. This study revealed that circRHOQ promotes yak IMF development via the SE-circRHOQ/miR-5093/IRF5 axis, thus providing a basis for further investigation into IMF deposition and improvement of high-altitude livestock breeds."

Journal • IRF5

BRD4 inhibition suppresses histone H4 UFMylation to increase ferroptosis sensitivity through TXNIP. (PubMed, Cell Death Dis) - "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."

Journal • Oncology • Solid Tumor • BRD4 • DDRGK1 • MYC • TXNIP

The Spop/BRD4/c-Myc Axis Modulates IMiDs Sensitivity in Multiple Myeloma (ASH 2023) - "The development of novel agents including immunomodulatory drugs (IMiDs) lenalidomide (Len) and pomalidomide (Pom) has led to improved patient outcomes in multiple myeloma (MM); however, MM patients inevitably experience relapse and drug resistance. We found that combination treatment with JQ-1 and IMiDs reversed IMiDs resistance of SPOP KO MM cell lines and primary MM cells from relapsed patients. Our data show that SPOP is a CRBN-independent modulator of IMiDs sensitivity by regulating the BRD4/c-Myc axis and provides the preclinical rationale for combining IMiDs with BRD4 inhibitors to overcome IMiDs resistance and improve patient outcomes."

Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma • Targeted Protein Degradation • BRD4 • CRBN • IKZF1 • IKZF3 • IRF4 • MYC • SPOP

The RNA-binding protein RBM39 scaffolds an m⁶A-dependent RNA decay complex that destabilizes Tat transcripts and restricts HIV-1 reactivation. (PubMed, PLoS Biol) - "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."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology • Targeted Protein Degradation • CD4 • DDX5 • RBM39 • YTHDC1

Development and Efficacy of a Novel Bromodomain and Extraterminal Domain Degrader K-256 in MYC/BCL2-Related Lymphoma (ASH 2023) - "The GI50 of K-256 in SU-DHL4 and SU-DHL6 was 12.8 nM and 7.50 nM, respectively, and K-256 induced cell death at lower concentrations than existing drugs (vs. JQ1, OTX-015, and ABBV-075, p < 0.0001; vs. dBET6 and ARV-771, p < 0.01)...As expected, the combination of K-256 with venetoclax also demonstrated synergistic effects in PDX cells, similar to those observed in cell lines (CI of 0.515 to 0.762 for inhibiting cell proliferation; 0.085 to 0.995 for inducing apoptosis)... The novel BET degrader, K-256, bound to BET proteins at lower concentrations than existing BET inhibitors and degraders, strongly suppressing MYC expression, primarily via BRD4 degradation. Additionally, K-256 demonstrated superior therapeutic effects in MYC/BCL2-related PDX models both in vitro and in vivo, suggesting that this novel drug could be a promising therapeutic agent for MYC/BCL2-related lymphoma. Its translation to future clinical applications warrants further consideration."

Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BRD2 • BRD3 • BRD4 • BRDT • MYC

Tumor Suppressive Mir-7 Targeting PSME3 Improves the Efficacy of Histone Deacetylases Inhibitors in Multiple Myeloma (ASH 2023) - "1S, KMS-11, RPMI-8226, H929, and U266) and patient samples to 10 nM panobinostat and 1 µM vorinostat for 48 h, we performed quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and observed significant downregulation in the expression of miR-7...1S and KMS-11 cells to the BRD4 inhibitor JQ1, which suppresses MYC, at concentrations of 50 and 100 nM for 48 h, qRT-PCR showed that the expression of miR-7 was significantly downregulated in these cell lines...The favorable combination effect of bortezomib with HDAC inhibitors could be due to the modulation of the miR-7- PSME3 axis... We revealed that miR-7 exerts anti-myeloma effects and that PSME3 is one of the targets of miR-7. miR-7 is an interesting microRNA because it is positively regulated by MYC, even though it is tumor-suppressive. Elucidating the role of miR-7 may lead to the re-discovery of HDAC inhibitors in MM therapeutic strategies."

Clinical • Epigenetic controller • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • BRD4 • LRRC59 • MIR7 • MYC

Super-Enhancer-Driven IGF2BP2 and IGF2BP3 Promote DDX21 Expression in Acute Myeloid Leukemia (ASH 2023) - "BRD4 inhibitor JQ1 or BRD4 knockdown could lead to the suppression of IGF2BP2/3 expression, indicating the activation by SE machinery on the transcription of IGF2BP2/3... Dysregulation of SE-IGF2BP2/IGF2BP3-DDX21 axis promotes the progression of AML, which paves the way to develop more effective therapeutic strategies."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BRD4 • DDX21 • IGF2BP2 • IGF2BP3

Investigation of the Synergistic Combination of a Novel Celmod (CC-99282) and BET Inhibitors in Preclinical DLBCL (ASH 2023) - P1/2 | "Similar synergistic effects were found when combining GOLCA with JQ1, another tool compound BET inhibitor, confirming BET inhibition potentiates the anti-DLBCL effects of the CELMoD agent. BET inhibition potentiates anti-proliferative effects of GOLCA in DLBCL cells through synergistic induction of p21 and inhibition of E2F signaling. The synergetic effects of BMS-986158 and GOLCA suggest potential clinical benefits of combining lower doses of single agents to achieve better efficacy with reduced risk of adverse effects."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • AURKA • BRD4 • CDC45 • CDKN1A • CHEK1 • CRBN • E2F1 • IKZF1 • IL17RB • SKP2

Reclassification of ETS Family Transcription Factor Fusions in Pediatric AML Based on Molecular Drivers (ASH 2023) - "Preliminary in vitro data in ETS cell lines with an enhanced MYC transcriptional signature (YNH-1, TSU-1621) suggests that the BET bromodomain inhibitor JQ1 may dampen MYC and induce anti-proliferative effects...Overall, reclassification based on molecular drivers appears to not only be more accurate in predicting relapse and final outcome, but also in proposing novel agents for pAML patients who overwhelmingly do not respond to standard regimens. Reinvigoration of immune recognition by inhibition of EZH2 and/or inhibition of MYC-driven proliferation via BET inhibitors may prove an essential step in setting the stage for successful HSCT for a significant portion of pAML ETS patients."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • CCND3 • EP300 • ETV6 • EWSR1 • FLI1 • FUS • IFIT2