apabetalone (RVX 208) / Resverlogix - LARVOL DELTA

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

Lysine-targeting, Covalent Inhibitors of Bromodomain BD1 of BET Proteins in Live Cells and Animals. (PubMed, Angew Chem Int Ed Engl) - "By further introducing EBA and salicylaldehyde into PLX51107 (a noncovalent BETi), we generated lysine-reactive, irreversible (BDS1-4) and reversible (BDS5-6) BD1 covalent inhibitors. Importantly, BDS4 retained robust activity against fibrosis in cells and animals when compared to RVX-208 (a reported BD2-selective noncovalent inhibitor) which showed only marginal effects. Our work serves as a useful tool to delineate distinct functions of BD1 and BD2 in future studies."

Journal • Fibrosis • Immunology • Oncology • BRD4

A Study of Apabetalone in Subjects With Long -COVID (clinicaltrials.gov) - P2/3 | N=200 | Recruiting | Sponsor: Resverlogix Corp | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2025 ➔ Mar 2026 | Initiation date: Nov 2024 ➔ Apr 2025 | Trial primary completion date: Jul 2025 ➔ Dec 2025

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Type 2 Diabetes Mellitus

Orally Bioavailable BRD4 BD1 Inhibitor ZL0516 Effectively Suppresses Colonic Inflammation in Animal Models of Inflammatory Bowel Disease. (PubMed, ACS Pharmacol Transl Sci) - "Also, we found that RVX208, a selective BRD4 BD2 inhibitor in Phase III clinical development, only displayed marginal effects in these IBD animal models. Collectively, our results demonstrate that specific BRD4 BD1 inhibition is a novel therapeutic strategy for IBD-associated colonic inflammation, and orally effective inhibitor ZL0516 is a promising candidate for the development of a novel therapeutic regimen against IBD."

Journal • Preclinical • Developmental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • BRD4 • TNFA

The Use of Apabetalone in Reducing Cardiovascular Outcomes, Based on the Current Evidence and Trials. (PubMed, Eur Cardiol) - "The primary endpoint was the composite of cardiovascular death, MI and stroke. This article explores the various clinical research and outcomes related to apabetalone and its use in the context of its proposed mechanism."

Journal • Review • Acute Coronary Syndrome • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus

A combinatorial screening protocol for identifying novel and highly potent dual-target inhibitor of BRD4 and STAT3 for kidney cancer therapy. (PubMed, Front Pharmacol) - "Moreover, in vivo experiments revealed that BST-4 more effectively inhibited the growth of xenograft tumors compared with positive controls RVX-208 and CJ-1383. Overall, these data indicated that BST-4 could be a promising candidate compound for RCC therapy."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Solid Tumor • BRD4 • STAT3

The Bromodomain and Extraterminal Protein Inhibitor Apabetalone Ameliorates Kidney Injury in Diabetes by Regulating Cholesterol Accumulation and Modulating the Gut Microbiota. (PubMed, Kidney Int Rep) - "Therefore, we suggest that apabetalone showed significant antihyperlipidemic and antifibrotic effects, closely associated with alterations in the gut microbiota and cholesterol metabolism. The results of this investigation provide fresh perspectives on the processes that underlie apabetalone's effects in db/db mice."

Journal • Diabetes • Diabetic Nephropathy • Fibrosis • Gastrointestinal Disorder • Immunology • Metabolic Disorders • Nephrology • Renal Disease • ABCA1 • APOA1 • BRD4 • PPARG

Apabetalone alleviates ligature-induced periodontitis by inhibiting M1 macrophage polarization via an immunometabolic shift. (PubMed, Int Immunopharmacol) - "Collectively, these findings indicate that apabetalone improves the periodontal immune microenvironment by regulating metabolites in macrophages. Apabetalone exerts anti-inflammatory and osteo-protective effects by replenishing the broken TCA cycle and suppressing glycolysis. Apabetalone is a potential candidate for the treatment of periodontitis."

Journal • Dental Disorders • Inflammation • Osteoporosis • Periodontitis • HK2 • PFKFB3

Epigenetic mechanisms mediate cytochrome P450 1A1 expression and lung endothelial injury caused by MRSA in vitro and in vivo. (PubMed, FASEB J) - "Epigenetic inhibitors (C646, RVX-208) reduce MRSA-induced CYP1A1 expression and inflammatory responses, including cytokine release and adhesion molecule expression...Analysis of publicly available data suggests upregulation of CYP1A1 expression in ARDS patients compared to ICU controls. In summary, these studies provide new insights into MRSA-induced lung injury and identify a novel functional role for epigenetic upregulation of CYP1A1 in lung EC during ARDS pathogenesis."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • CYP1A1

Apabetalone: evaluating cardiovascular and safety outcomes in meta-analysis (AHA 2024) - "Our meta-analysis highlights the significant impact of apabetalone on certain lipid parameters and adverse events. However, it did not demonstrate significant effects on all-cause mortality or non-fatal MI. Further well-designed and reported RCTs were warranted to elucidate the clinical implications of apabetalone in selected group of patients that might benefit the most from apabetalone that may also improve cardiovascular disease management."

Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Myocardial Infarction • APOA1

Apabetalone Protects Against Heart Failure with Preserved Ejection Fraction by Suppressing Myocardial Inflammation (AHA 2024) - "Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Inflammation • BRD4 • IL1B • TNFA

A Study of Apabetalone in Subjects with Long -COVID (clinicaltrials.gov) - P2/3 | N=200 | Not yet recruiting | Sponsor: Resverlogix Corp

New P2/3 trial • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Type 2 Diabetes Mellitus • CD27 • CD4 • CD8 • IFNG • IL10 • IL12B • IL17A • IL18 • IL1A • IL1B • IL2 • IL33 • IL6 • MIR146A • MMP1 • MMP9 • TNFA

Targeting BRD4-HK2 reverses perivascular adipose tissue meta-inflammation shift and rescues cardiometabolic vascular dysfunction (EASD 2024) - "Materials and We assessed the contribution of BRD4, by acute pharmacological inhibition via the BRD4 inhibitor RVX-208, to ex-vivo microvascular and perivascular adipose tissue (PVAT) function in fat biopsies from healthy volunteers (n=16) and patients with obesity and hypertension (n=16)... We identified BRD4-HK2 interaction at the PVAT level as a novel mediator of cardiometabolic damage. Its targeting rescues vascular dysfunction by reversing the PVAT meta-inflammatory shift. Epigenetic modulators of meta-inflammation may represent a promising strategy in patients with obesity and hypertension."

Metabolic Disorders • Obesity • BRD4 • HK2 • IL1B

Effects of BET Inhibition on lung micro-environmental changes in obesity-related pulmonary Arterial Hypertension (PAH) (ESC 2024) - "Apabetalone (APA), a selective inhibitor of bromodomain and extra-terminal containing protein family (BET) proteins, prevents bromodomain-containing protein 4 (BRD4) interactions with chromatin thus modulating gene expression... APA is able to reset the lung micro-envirnment in obesity thus reducing inflammation and senescence. BET inhibitors could represent potential therapeutic approaches in this setting."

Cardiovascular • BRD4 • HIF1A • IL1B • IL6 • NOX4 • RELA • TGFB1 • TNFA

Targeting BRD4-HK2 reverses the meta-inflammatory shift in perivascular adipose tissue and rescues cardiometabolic vascular dysfunction. (ESC 2024) - "We assessed the ex vivo effects of BRD4 inhibition on vascular function by pressure myography in the presence or absence of perivascular adipose tissue (PVAT), at baseline and after incubation with the BRD4 inhibitor RVX-208 or with anti-inflammatory/anti-metabolic drugs... We identified BRD4-HK2 interaction at the PVAT level as a novel mediator of cardiometabolic damage. Its targeting rescues vascular dysfunction by reversing the PVAT meta-inflammatory shift. Epigenetic modulators of meta-inflammation may represent a promising strategy in patients with obesity and hypertension."

Cardiovascular • Hypertension • BRD4 • HK2 • IL1B

The BET inhibitor Apabetalone protects against heart failure with preserved ejection fraction by suppressing myocardial inflammation (ESC 2024) - "Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF."

Cardiovascular • Congestive Heart Failure • Heart Failure • BRD4 • IL1B • TNFA

Epigenetic BET inhibitor apabetalone counters inflammatory and fibrotic processes in activated cardiac fibroblasts providing insight into reduced hospitalizations for heart failure in BETonMACE trial (ESC 2024) - "In vitro, APA treatment reduced proinflammatory crosstalk between monocytes and CFs, resulting in less monocyte migration, monocyte - CF adhesion and CF contraction. APA also reduced signaling by TGF-β1, thus reducing profibrotic and contractile behaviour of CFs responsible for cardiac fibrosis. Since fibrosis contributes to HF, this data provides insight into the observed reduction in hospitalization due to HF in the BETonMACE trial."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • CCL2 • IFNG • IL1B • POSTN • TGFB1 • TNFA • VCAM1

The BET protein inhibitor apabetalone (RVX-208) prevents doxorubicin-induced endothelial senescence (ESC 2024) - "Targeting BET proteins with RVX-208 may offer a promising therapeutic strategy to prevent endothelial aging in cancer patients undergoing cardiotoxic therapies."

Cardiovascular • BRD4 • CCL2 • CDKN1A • CDKN1C • COL1A2 • CXCL8 • IL6 • TIMP2 • TP53

Correspondence: Reply to commentary on "Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis". (PubMed, Pharmacol Res) - No abstract available

Journal • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • PLK1

Exploring the Therapeutic Potential of Apabetalone in Diabetic Kidney Disease: Bridging Preclinical Findings with Clinical Translation. (PubMed, Pharmacol Res) - No abstract available

Journal • Preclinical • Diabetic Nephropathy • Nephrology • Renal Disease

Commentary on "Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis". (PubMed, Pharmacol Res) - No abstract available

Journal • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Renal Disease • PLK1

Commentary on "Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis". (PubMed, Pharmacol Res) - No abstract available

Journal • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Renal Disease • PLK1

Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis. (PubMed, Pharmacol Res) - "BRD4 regulates the P300/H3K27ac/PLK1 axis, leading to the activation of the NLRP3 inflammasome and subsequent cell pyroptosis, inflammation, and fibrosis. These results may provide new perspectives on DKD treatment."

Journal • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • BRD4 • NLRP3 • PLK1

Combined Inhibition of Histone Deacetylases and Bromodomain Proteins Normalizes Gene Expression and Reverses Sugen/Hypoxia-induced Pulmonary Hypertension (ATS 2024) - "Cells were treated with HDACi (OKI-5) or BRDi (JQ1) or the combination of both. Combination of HDACi and BRDi in low doses is effective in normalizing the persistent activation of PH-Fibs and improving hemodynamics and pulmonary vascular remodeling in Sugen/hypoxia PH rats, offering promise for epigenetic-targeted combination therapies in PAH."

Epigenetic controller • IO biomarker • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • BCL2 • BRD4 • CDKN1A • CXCL12