apabetalone (RVX 208) / Resverlogix - LARVOL DELTA

BET inhibitor apabetalone suppresses the fibrotic activation of cardiac fibroblasts associated with heart dysfunction. (PubMed, Biomed Pharmacother) - "Apabetalone reduced cytokine-mediated profibrotic FB activation in vitro and ex vivo, demonstrating therapeutic potential for adverse cardiac remodeling that contributes to cardiac dysfunction and HF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • IL1B • MEOX1 • POSTN • TGFB1

Epigenetic reprogramming of lung fibroblasts drives pulmonary hypertension in obesity-related HFpEF (ESC 2026) - "Fibroblasts in PH-obHFpEF acquire a pathogenic, epigenetically reprogrammed phenotype that amplifies inflammation, endothelial dysfunction, and fibrotic remodeling. BET inhibition with apabetalone re-establishes fibroblast quiescence, dampens pathological intercellular signaling, and mitigates pulmonary hypertension development."

Cardiovascular • Congestive Heart Failure • Heart Failure • ACVRL1 • NTF3 • TNFRSF11B

Epigenetic remodeling drives autophagy dysfunction in cardiometabolic HFpEF (ESC 2026) - "BET inhibition with RVX-208 restored autophagy-related transcriptional programs and significantly improved diastolic function and exercise capacity.ConclusionsBET-mediated epigenetic remodeling in cardiomyocytes represents a central mechanism driving autophagy impairment in cHFpEF. Pharmacological BET inhibition restores autophagic signaling and improves cardiac function, highlighting BET proteins as potential therapeutic targets."

Cardiovascular • Congestive Heart Failure • Heart Failure

BET Inhibition with apabetalone restores cardiometabolic HFpEF through suppression of myocardial and systemic inflammation (ESC 2026) - "Conclusions In mice and patients, we show for the first time that the FDA approved BET inhibitor APA exerts significant beneficial effects in cHFpEF. Our results set the stage for validation in large preclinical models and clinical trials testing APA in patients with cHFpEF."

Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • BRD4 • IL1B • IL6 • TNFA

Chromatin readers orchestrate doxorubicin-induced endothelial senescence and paracrine cardiotoxicity: towards epi-drugs in cardio-oncology (ESC 2026) - " Human aortic endothelial cells (ECs) were exposed to DOXO (50–500 nM) in the presence or in the absence of the selective BET inhibitor Apabetalone (RVX-208)... BET-driven transcriptional programs are heavily implicated in DOXO-induced ECs damage. BET inhibitors may represent promising drugs to mitigate cardiovascular dysfunction in cardio-oncology patients."

Cardiovascular • BRD2 • BRD4 • CDKN1A • KLF4 • MYC • NANOG

Apabetalone Drives a Metabolic Shift Towards Ketogenesis and Reduces Liver Steatosis in Diet-Induced Obesity Mice. (PubMed, Biomedicines) - " Apabetalone improves hepatic lipid handling, favoring ketogenesis. As ketones have demonstrated beneficial effects on cardiac function, increased ketones induced by apabetalone may not only contribute to the observed attenuation of FS in patients, but also a reduction in cardiac events among patients with high likelihood of MASLD, as well as in the overall trial population."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Genetic Disorders • Heart Failure • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

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

Apabetalone mediates HIV-1 transcriptional activation and clearance of latently infected cells via LncRNA OSER1-AS1. (PubMed, Gene) - "Apabetalone enhances HIV-1 transcription by upregulating OSER1-AS1 expression, thereby promoting Tat-CDK9 binding."

Journal • Human Immunodeficiency Virus • Infectious Disease • CDK9 • CDKN1A

BET-induced metabolic reprogramming fuels inflammation at the vascular-fat interface in mice and patients with cardiometabolic disease. (PubMed, Cell Rep) - "Using vessels from mice and patients with CMD, we show that pharmacological inhibition of BET proteins by RVX-208 prevents the maladaptive crosstalk between perivascular adipose tissue (PVAT) and blood vessels...Pharmacological inhibition of HK2 in vessels from cardiometabolic patients restored endothelial-dependent vasorelaxation. This unveiling of a BET/HK2-dependent crosstalk between PVAT and blood vessels highlights the potential of therapeutic strategies to prevent vascular damage in cardiometabolic patients."

Journal • Preclinical • Cardiovascular • Inflammation • Metabolic Disorders • HK2

Epigenetic BET protein signaling drives autophagy dysfunction in HFpEF (HEART FAILURE 2026) - "Importantly, BET inhibition with RVX-208 restored autophagy-related transcriptional programs and significantly improved diastolic function and exercise capacity. Conclusions These findings identify a BET-driven epigenetic mechanism regulating autophagy in cHFpEF and demonstrate that pharmacological BET inhibition restores autophagic signaling and improves cardiac function, supporting BET proteins as therapeutic targets in HFpEF."

Cardiovascular • Congestive Heart Failure • Heart Failure

Immunotherapies based on macrophage reprogramming in periodontitis and apical periodontitis. (PubMed, Clin Oral Investig) - "Immunotherapeutic approaches targeting macrophage polarization could complement conventional biofilm control with emphasis on regenerative periodontics and endodontic procedures, opening new avenues for biologically driven, patient-centered therapies."

IO biomarker • Journal • Review • Dental Disorders • Immunology • Inflammation • Osteoporosis • Periodontitis • CCL2 • CD163 • CD8 • CD80 • HIF1A • MIR126 • MRC1

A resveratrol derivative RVX-208 inhibits PD-1/PD-L1 to restrain non-small cell lung cancer as an immunotherapy. (PubMed, Biochem Pharmacol) - "Consistent with these findings, RVX-208 treatment also reduced PD-1 levels in T cells from tumor bearing mice in vivo. Collectively, these results identify RVX-208 as a promising small-molecule immunotherapeutic agent for the treatment of lung cancer."

IO biomarker • Journal • Atherosclerosis • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • JAK2 • PD-L1

The Selective Bromodomain and Extra-Terminal Domain (BET) Inhibitor RVX-208 Reduces Cocaine-Seeking Behaviour and Alters Proteomic Pathways in the Nucleus Accumbens. (PubMed, Addict Biol) - "Proteomic analysis of the NAc revealed that RVX-208 modulated several proteins, including those associated with dopamine activity (DRD1 and SLC6A3), transcriptional regulation (NFKB1), glutamate transport (SLC1A2) and ion channel activity (KCNJ10), and many changes were sex-dependent. Collectively, these findings indicate that domain-selective BET inhibition is effective at reducing cocaine-seeking behaviour and point to novel mechanisms that may contribute to its therapeutic effect."

Journal • CNS Disorders • SLC1A2 • SLC6A3

BET inhibitors in cardiovascular diseases: from atherosclerosis to heart failure. (PubMed, Pharmacol Rep) - No abstract available

Journal • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Brd4 BD1 Domain Antagonism of MS436 Preserves Blood-Brain Barrier Integrity via Rnf43/β-Catenin Signaling Pathway. (PubMed, Adv Sci (Weinh)) - "Crucially, opposing BBB effects of domain-specific BET antagonism: the BD2 antagonist RVX208 disrupt the BBB, whereas the BD1 antagonist MS436 significantly reduces leakage and improves neurological outcomes, revealing therapeutic potential is demonstrated...This defines a novel Brd4 BD1/Rnf43/β-catenin axis essential for BBB integrity. The findings establish Brd4 BD1 inhibition as a novel BBB-protective strategy and position MS436 for repurposing in cerebrovascular diseases, necessitating reevaluation of domain-specific BET targeting for neurovascular pathologies."

Journal • CNS Disorders • Oncology • Targeted Protein Degradation • Vascular Neurology • BRD4 • CTNNB1 • RNF43

Inhibition of bromodomain and extra-terminal motif (BET) proteins in pediatric sarcoma: A systematic review of in vitro and in vivo studies. (PubMed, Drug Discov Today) - "Accordingly, we reported that ABBV-744 and RVX-208, which selectively target the BD2 domain, and GNE-987, a specific BRD4 degrader, are the most promising inhibitors. However, ABBV-075, a pan-BETi, also exhibits high efficacy, being effective at low doses. Nevertheless, translating these experimental findings into clinical practice remains difficult because of resistance, toxicity, and inconsistent responses. Future approaches include using biomarkers for patient selection, developing isoform-specific BETi, and designing rational combination therapies to enhance treatment for these aggressive pediatric cancers."

Journal • Preclinical • Review • Oncology • Pediatrics • Sarcoma • Solid Tumor • BRD4

The epi-drug RVX-208 restores autophagy in cardiometabolic heart failure with preserved ejection fraction (ESC-WCC 2025) - "Autophagy was impaired in cHFpEF mice, as indicated by the upregulation of mTOR signaling and reduced expression of autophagosome genes Atg7 and Atg13. Single-nucleus RNA sequencing (snRNA-seq) identified four main clusters of cardiomyocytes, each exhibiting suppressed autophagic pathways. Gene expression profiling revealed significant dysregulation of autophagic flux-related genes, including Atg5, TMEM74, and PS6K (involved in mTOR signaling)."

Cardiovascular • Congestive Heart Failure • Heart Failure • ATG5 • ATG7 • BRD2 • BRD4

Therapeutic modulation of the lung microenvironment in obesity-induced heart failure with preserved ejection fraction (ESC-WCC 2025) - "Control and obHFpEF mice were chronically treated with the BET protein inhibitor Apabetalone (APA) for 14 days... APA can reset the lung microenvironment in a mouse model of obese HFpEF, thus reducing inflammation, cellular senescence and microvascular endothelial dysfunction. BET inhibitors may be promising epi-drugs to treat or prevent PH development in obese HFpEF"

Cardiovascular • Congestive Heart Failure • Heart Failure • HIF1A • NOX4

The BET protein inhibitor Apabetalone rescues cardiometabolic heart failure with preserved ejection fraction by suppressing myocardial and systemic inflammation: a study in mice and humans (ESC-WCC 2025) - "In mice and patients, we show for the first time that the FDA approved BET inhibitor APA exerts significant beneficial effects in cHFpEF. Our results set the stage for validation in large preclinical models and clinical trials testing APA in patients with cHFpEF."

Preclinical • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • BRD4 • IL1B • IL6 • TNFA

Epigenetic editing of chromatin readers rescues doxorubicin-induced endothelial senescence and vascular dysfunction (ESC-WCC 2025) - "Targeting BET proteins may prevent endothelial aging and vascular dysfunction in cancer patients undergoing cardiotoxic therapies."

Cardiovascular • BRD2 • BRD4 • KLF4 • MYC • NANOG

BET protein inhibition rewires the vascular-fat interface in cardiometabolic disease (ESC-WCC 2025) - "In humans, we assessed the impact of ex-vivo BRD4 inhibition on vascular function by RVX-208 (an FDA-approved BRD4 inhibitor) in small vessels (100-300 μM) dissected from omental fat biopsies... Inhibition of BRD4 downregulates HK2 while reversing pro-glycolytic changes and triglyceride accumulation in PVAT, thus rescuing vascular dysfunction. The unveiling of a BET-dependent cross-talk between PVAT and blood vessels supports therapeutic strategies to prevent vascular disease in cardiometabolic patients."

Cardiovascular • Hypertension • BRD4 • HK2 • IL1B • IL6

Targeting the Kynureninase-HDAC6-Complement Axis as a Novel Therapeutic Strategy in Glioblastoma. (PubMed, Epigenomes) - "In vitro studies in GBM cell lines (U87, U251, T98G) assessed the effects of KYNU silencing and treatment with an HDAC6 inhibitor (tubastatin) and a BET inhibitor (apabetalone) on gene expression and cell viability... Our findings establish the KYNU-HDAC6-complement axis as a critical regulatory pathway in GBM. Targeting KYNU-mediated complement activation through combined epigenetic approaches-such as HDAC6 and BET inhibition-represents a promising strategy to overcome complement-driven resistance in GBM therapy."

Journal • Brain Cancer • Gene Therapies • Glioblastoma • Oncology • Solid Tumor • KYNU

Development of a Vessel-on-a-Chip as a Viral Infection Model and Antiviral Drug Screening Platform with Viral Mimics. (PubMed, ACS Biomater Sci Eng) - "To mimic viral infections, inflammation was induced using virus-mimicking particles, specifically polyinosinic-polycytidylic acid, while anti-inflammatory drugs RVX-208, JQ-1, and PFI-1 were evaluated for their therapeutic potential in reducing inflammation. Combining the results from VCAM-1 intensity measurements and vascular diameter changes in drug-treated cases, the effective dose of each drug was suggested. This vessel-on-a-chip platform demonstrates significant potential for advancing studies on vascular pathophysiology and antiviral treatments, offering convenient approaches for investigating both viral agents and therapeutic drugs."

Journal • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases • VCAM1

Employing epi-drugs to rescue lung microenvironmental changes in heart failure with preserved ejection fraction (HEART FAILURE 2025) - "Control and HFpEF-PH mice were chronically treated with the BET protein inhibitor Apabetalone (APA) for 14 days... APA can reset the lung microenvironment in a cardiometabolic model of HFpEF-PH, reducing inflammation and cellular senescence. BET inhibitors may be promising epi-drugs to treat PH in in HFpEF."

Cardiovascular • Congestive Heart Failure • Heart Failure • HIF1A • NOX4

Epigenetic editing of BET proteins restores autophagy and cardiac function in cardiometabolic heart failure with preserved ejection fraction (HEART FAILURE 2025) - "cHFpEF and control mice were treated with vehicle or with the selective BET inhibitor RVX-208 for 14 days...Pharmacological inhibition of BET proteins restores autophagic flux while improving cardiac function in cHFpEF mice. Our results set the stage for preclinical studies testing FDA-aproved BET inhibitors in the setting of HFpEF."

Cardiovascular • Congestive Heart Failure • Heart Failure • ATG7 • BRD2 • BRD4