bosentan / Generic mfg. - LARVOL DELTA

A patient-derived CRISPR platform reveals selective dependencies in Acute Myeloid Leukemia (ASH 2025) - "Our results indicate that EDNRAknockout inhibits AML cell proliferation and growth, highlighting its potential as a therapeutic target.Furthermore, EDNRA is overexpressed in AML compared to normal cells, and since FDA approved EDNRAinhibitors such as Macitentan, Bosentan, Ambrisentan, and Clazosentan are already being used to treatpulmonary arterial hypertension, this presents a promising opportunity to evaluate these inhibitors aspotential chemotherapy-sensitizing agents for high-risk AML.SOD1 plays a critical role in eliminating toxicradicals generated within biological systems and has been associated with poor outcomes in AML. This study demonstrates the establishment of a scalable platform for CRISPR screening inprimary AML cells for identification of more conserved vulnerabilities that may be exploitedtherapeutically, with EDNRA as a potential target. Ongoing work includes validating key targets with thegoal of advancing therapeutic strategies. Future studies will..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pulmonary Arterial Hypertension • Respiratory Diseases • EDNRA • HOXA9 • MEIS1 • PPM1D • SUZ12

Exploring the potential of liver microphysiological systems of varied configurations to model cholestatic chemical effects. (PubMed, Arch Toxicol) - "Upon exposure to cholestatic agents (bosentan, 2-octynoic acid, α-naphthyl isocyanate), robust CYP3A4 induction was observed in HepaRG and PHH treated with bosentan and α-naphthylisocyanate...In summary, the hepatocyte functional markers (CYP3A4, albumin, urea) were comparable between PHH and HepaRG in 2D and PhysioMimix LC12 MPS. However, the effects of cholestatic agents on PHH and HepaRG, specifically, bile acid release were detected only in the PhysioMimix LC12 with PHH showing more consistent responses compared to HepaRG."

Journal • Cholestasis • Hepatology • CYP3A4

Selection of Endothelin Receptor Antagonists in the Treatment of Pulmonary Arterial Hypertension: A Comprehensive Narrative Review. (PubMed, Adv Ther) - "Endothelin receptor antagonists (ERAs) are established treatments for PAH, and three agents-bosentan, ambrisentan, and macitentan-are approved for use in adults in the USA. It also discusses the differing physicochemical and pharmacokinetic properties of each ERA and how these unique characteristics influence their receptor binding and kinetics, mechanisms of action, therapeutic effects, dosing frequency, and safety in PAH. In the absence of head-to-head clinical trials assessing their comparative efficacy and safety, it is important to understand both the similarities and the distinguishing characteristics of the three ERAs approved in PAH, to inform individualized treatment selection."

Journal • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

The Involvement of the Peptidergic Systems in Breast Cancer Development. (PubMed, Cancers (Basel)) - "Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1-7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin)...Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9-39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review...Taken together, the available data highlight the enormous promise..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • GRP-10

Comparative Analysis of Species-Specific Hepatocyte Function and Drug Effects in a Liver Microphysiological System PhysioMimix LC12 and 96-Well Plates. (PubMed, ACS Pharmacol Transl Sci) - "Also, cells were exposed to species-specific hepatotoxicants such as bosentan (BOS), fialuridine (FIAU), and a common hepatotoxicant for all species, chlorpromazine (CPZ)in both PhysioMimix LC12 and traditional 2D cultures. Still, variability and low throughput are limitations of MPS for prospective studies of species-specific responses. Overall, this study confirms the utility of liver safety studies using PhysioMimix LC12 and also provides suggestions for experimental designs to overcome the limitations of more complex test systems."

Journal • Hepatology • Liver Failure

The Neurogenic Inflammation Mediator Endothelin-1 Causes Human Skin Barrier Disruption in Atopic Dermatitis via an ETAR/TRPA1-Axis. (PubMed, Allergy) - "Our findings suggest that a neurogenic inflammation axis ET-1/ETAR/TRPA1 contributes to skin barrier impairment in AD by repressing differentiation markers and tight junction proteins. Additionally, we demonstrate ETAR-blockage as a rational therapeutic modality for patients with AD."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pain • CLDN1 • CLDN4 • EDN1 • FLG • IL1B • IL6 • LORICRIN • OCLN • TNFA • TRPA1

Long-Term Erythrocytapheresis Did Not Prevent Development of Severe Pulmonary Hypertension in Sickle Cell Disease (ASH 2023) - "She had previously failed hydroxyurea therapy...She was initiated on anticoagulation therapy with enoxaparin, sildenafil, and bosentan...This patient had a history of nocturnal hypoxemia and OSA, which some studies indicate are associated with pulmonary hypertension in adolescents with SCD. Screening for nocturnal hypoxemia and OSA is recommended in SCD to identify patients at high risk of PH development [2]."

Cardiovascular • Cough • Genetic Disorders • Heart Failure • Hematological Disorders • Hepatology • Hypertension • Obstructive Sleep Apnea • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • Sickle Cell Disease • Sleep Disorder

A Case of Atypical Hemolytic Uremic Syndrome and Scleroderma Renal Crisis Successfully Treated with Ravulizumab (KIDNEY WEEK 2025) - "She was initially treated with eculizumab then ravulizumab leading to remission...For her scleroderma maintenance therapy, she remains on Rituximab and myfortic with close monitoring by her rheumatologist...Scleroderma renal crisis is typically treated with ACE inhibitors, and more experimental therapies include plasma exchange therapy, bosentan, and prostacyclin. Given that scleroderma renal crisis and aHUS are both likely triggered by an overactive complement system, it is reasonable that these conditions can be associated with one another and treated with complement inhibitors. This case illustrates yet another example of safe long-term maintenance therapy on a long-acting C5 complement inhibitor in a case of scleroderma renal crisis and aHUS."

Clinical • Acute Kidney Injury • Anemia • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Complement-mediated Rare Disorders • Congestive Heart Failure • Fatigue • Heart Failure • Hematological Disorders • Hypertension • Immunology • Nephrology • Renal Disease • Rheumatology • Scleroderma • Systemic Sclerosis

Severe Pulmonary Hypertension in a Young Adult with Congenital Diaphragmatic Hernia: A Challenging Case of Multifactorial Developmental Lung Disease. (AHA 2025) - "He developed severe PH requiring extracorporeal membrane oxygenation (ECMO), prostaglandins, and prolonged dual therapy with endothelin receptor antagonists (bosentan, macitentan)...At age 20, clinical deterioration followed the introduction of selexipag, with worsening hypoxemia, increased oxygen requirements, and suspicion of pulmonary vascular disease progression...This case underscores the complex trajectory of PH in survivors of CDH and the risks associated with transitions in pulmonary vasodilator therapy. It highlights the need for long-term multidisciplinary follow-up and raises concerns about late-onset pulmonary vascular deterioration. Novel strategies and biomarkers are needed to better phenotype and risk-stratify this unique patient population.Use of AI tools:No automated editing assistance was used."

Clinical • Cardiovascular • Developmental Disorders • Gastroenterology • Psychiatry • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Optimizing Cardiovascular Outcomes in Hypertensive Patients with Obstructive Sleep Apnea: A Systematic Review of CPAP and Adjunctive Therapies (AHA 2025) - "Bosentan yielded a non-significant diastolic BP reduction (−3.1 mmHg; p = 0.101). Combination therapies-particularly CPAP with acetazolamide or ASV-may offer enhanced outcomes. Our findings support a tailored, multimodal treatment strategy and highlight the need for further large-scale RCTs evaluating non-CPAP interventions."

Clinical • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Novel Drug Molecules for Atherosclerosis from Ginkgo biloba, an Endangered Himalayan Herb, Via Pharmacoinformatics Approaches. (PubMed, Curr Pharm Biotechnol) - "The findings highlight the multi-target therapeutic potential of Isoginkgetin in mitigating the initiation and progression of atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • Inflammation • Metabolic Disorders • CYP19A1 • PACERR • PTGS2

Identification of sulfonamide drugs as allosteric inhibitor of Chikungunya virus envelope glycoprotein: An in silico approach for drug repurposing. (PubMed, Comput Biol Chem) - "These findings suggest bosentan's potential as a CHIKV inhibitor through allosteric modulation of E2 function. The study demonstrates the viability of targeting allosteric sites in CHIKV E2 and prioritizes bosentan for experimental validation as a repurposed antiviral therapy."

Journal • Chikungunya • Immunology • Inflammation • Rheumatology

Persistent Pulmonary Hypertension of the Newborn: A Pragmatic Review of Pathophysiology, Diagnosis, and Advances in Management. (PubMed, Biomedicines) - "This review details PPHN phenotypes, pathophysiology, etiology, diagnostics including echocardiography and biomarkers like B-type Natriuretic Peptide (BNP) or N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), and current therapeutic modalities, from lung recruitment and surfactant to targeted vasodilator therapy (iNO, sildenafil, milrinone, bosentan) and extracorporeal membrane oxygenation (ECMO). We emphasize the role of endothelial and molecular mechanisms in precision therapy and outline guidelines for clinical decision-making in diverse care settings."

Journal • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

EVALUATING THE COMPARATIVE EFFECTIVENESS OF ENDOTHELIN INHIBITORS IN IDIOPATHIC PULMONARY FIBROSIS: A COMPREHENSIVE BAYESIAN NETWORK META-ANALYSIS WITH INTERVENTION RANKING (CHEST 2025) - "This study suggests that bosentan and macitentan are the most effective endothelin inhibitors for managing idiopathic pulmonary fibrosis (IPF) in terms of improving disease progression and lung function, with higher SUCRA values indicating superior efficacy. Ambrisentan showed the least benefit across several outcomes, including FVC and DLCO. CLINICAL IMPLICATIONS: Clinicians may consider bosentan and macitentan as preferred options for managing IPF due their better efficacy profiles, particularly in slowing disease progression and improving lung function."

HEOR • Retrospective data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • EDN1

GROUP 3 PULMONARY HYPERTENSION IN A HYPOPLASTIC LEFT LUNG: A CASE REPORT (CHEST 2025) - "She was diagnosed as pulmonary hypertension group 3 and was started on bosentan... This case report highlights pulmonary hypertension (PH) as a complication of pulmonary hypoplasia in a 50 year-old female. Prognosis varies based on lung underdevelopment severity, malformations, and PH presence. Perinatal mortality is up to 70%, with survivors facing chronic lung disease and infections."

Case report • Clinical • Cardiovascular • Gastroenterology • Infectious Disease • Metabolic Disorders • Pneumonia • Preventive care • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Human blood vessel organoids as a model of vasculopathy in systemic sclerosis (ACR Convergence 2025) - "The endothelin receptor antagonist bosentan (BST) and the γ-secretase inhibitor DAPT were tested for their effects in preventing angiogenesis defects in BVOs. SSc-BVOs, but not healthy-BVOs demonstrated angiogenic defects, with decreased vessel density, vessel length and number of junctions, when exposed to SSc_aDU serum.Exposure of SSc-BVOs to SSc_aDU serum triggers concerted changes at epigenetic, mRNA and protein levels to induce upregulation of endothelial-to-mesenchymal transition (EndMT)-related pathways and proteins, such as αSMA, SNAIL1, TWIST1 and collagen synthesis, and downregulation of markers and pathways related to an endothelial cells (ECs) phenotype, such as CD31, VWF or tight junctions... This study demonstrates that SSc-BVOs recapitulate key features of SSc vasculopathy, including impaired angiogenesis and enhanced EndMT, increases in pathologic ECs populations, as well as loss of ECs -pericytes interactions when exposed to SSc_aDU serum. This study..."

Immunology • Scleroderma • Systemic Sclerosis • CD31 • PECAM1 • SNAI1 • TWIST1

Association Between Vasoactive-vasodilating Therapy and Reduced Detection of Pulmonary Arterial Hypertension in Systemic Sclerosis: Evidence from a EUSTAR Study (ACR Convergence 2025) - "Our data show that bosentan is associated with less frequent diagnosis of PAH and precapillary PH, in particular when employed in patients with current DU at the time of RHC. Our results support further research to optimize the timing and patient selection for VVD therapy in SSc, aiming also at additional preventive effects at pulmonary level."

Cardiovascular • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Dual Endothelin Receptor Inhibition with Bosentan Does Not Prevent the Early Formation of Post-Traumatic Joint Contracture in a Rat Model. (PubMed, J Clin Med) - "These findings suggest that, despite its potential in modulating fibrosis, bosentan does not mitigate the progression of the fibrotic condition. Furthermore, the involvement of endothelin-1 (ET-1) in the pathophysiology of PTJC remains yet to be fully understood, warranting further investigation."

Journal • Preclinical • Fibrosis • Immunology • Mood Disorders • Musculoskeletal Diseases • CTGF • EDN1 • IL6 • TGFB1

A Study in Healthy Men to Test How Bosentan Influences the Amount of Nerandomilast in the Blood (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

Predicting Food Effect On Oral Drug Absorption For Solubility-Epithelial Membrane Permeation-Limited Cases With Bile Micelle Solubilization. (PubMed, Pharm Res) - "FaRLS appropriately predicted the food effect for the SL-E drugs. The mechanism was experimentally confirmed by μFlux."

Journal

Comparative Effectiveness And Safety Of Soluble Guanylate Cyclase Stimulator Monotherapy Versus Combination With Endothelin Receptor Antagonists In Pulmonary Arterial Hypertension: A Multi-center Real-world Cohort Study (HFSA 2025) - "While guidelines recommend combination therapy, data comparing soluble guanylate cyclase stimulators (sGCs) alone versus in combination with endothelin receptor antagonists (ERAs) are limited. Using the TriNetX Research Network, we conducted a propensity score-matched cohort study of PAH patients receiving either sGC monotherapy (riociguat/vericiguat) or sGC+ERA combination therapy (with bosentan/ambrisentan/macitentan) between 2015-2023. In this real-world analysis, sGC+ERA combination therapy was associated with higher risks of MACE and hypotension compared to sGC monotherapy. However, after accounting for competing risks and patient characteristics, combination therapy showed potential mortality benefits. These findings emphasize the complex risk-benefit profile of combination therapy and underscore the importance of individualized treatment approaches in PAH management, with careful consideration of patient-specific factors to optimize outcomes."

Clinical • HEOR • Monotherapy • Real-world • Real-world evidence • Cardiovascular • Hypotension • Pulmonary Arterial Hypertension • Respiratory Diseases

Effects of sildenafil and metformin on endothelin-1 in the progression of pulmonary hypertension. (PubMed, Open Vet J) - "Currently, only sildenafil and bosentan have been approved by the Food and Drug Administration for the medical treatment of pediatric patients...Right heart catheterization was performed on day 22 after anesthesia with ketamine 50 mg/kg BW and xylazine 5 mg/kg BW intramuscularly...Sildenafil and metformin alone or in combination improve mPAP and ET-1 levels. Sildenafil plus metformin prevents artery remodeling in the PH model."

Journal • Anesthesia • Cardiovascular • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • EDN1

ACTION: The Impact of ERA Switching on Risk Stratification in Pulmonary Arterial Hypertension (clinicaltrials.gov) - P=N/A | N=121 | Recruiting | Sponsor: University of Sao Paulo General Hospital | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2026 ➔ Dec 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MoD: Mono vs. Dual Therapy for Pediatric Pulmonary Arterial Hypertension (clinicaltrials.gov) - P3 | N=100 | Active, not recruiting | Sponsor: Johns Hopkins University | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ May 2026 | Trial primary completion date: Sep 2026 ➔ May 2026

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Clinical, Biological, and Histological Features of Severe Drug Reactions: A Retrospective Study of 10 Cases (EADV 2025) - "Three patients with rheumatoid arthritis developed DRESS syndrome in response to methotrexate, erythromycin, and Non-steroidal anti-inflammatory drugs (NSAIDs). One patient with multiple autoimmune syndrome developed Lyell's syndrome following Bosentan and died... This study highlights the clinical and histological diversity of severe drug reactions, with lymphocytic and eosinophilic infiltration being the most common findings. The presence of neutrophilic infiltration and keratinocyte necrosis may indicate more severe forms. Visceral involvement, such as hepatocellular damage, cholestasis, and renal failure, was frequent, underscoring the need for rapid multidisciplinary intervention."

Retrospective data • Cholestasis • Eosinophilia • Hepatology • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Psoriasis • Psoriatic Arthritis • Renal Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Steven-Johnson Syndrome • Systemic Lupus Erythematosus • Tuberculosis