tezosentan (ACT-050089) / Roche - LARVOL DELTA

Endothelin-Dependent Myocardial Dysfunction in an Experimental Endotoxic Shock Model. (PubMed, Turk Kardiyol Dern Ars) - "Myocardial contractility impairment in experimental endotoxic shock occurs only in the presence of an intact coronary vasculature and is prevented by endothelin receptor blockade. These findings suggest that vascular endothelium-derived endothelin plays a key role in myocardial depression during endotoxic shock, whereas nitric oxide appears to have a limited contribution in this model."

Journal • Cardiovascular • CNS Disorders • Depression • Psychiatry • Septic Shock

Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes. (PubMed, J Clin Med) - "Backgroud: This study investigates the potential of vasodilator drugs as additive therapy in the treatment of urological cancers, particularly in combination with the antineoplastic agent 5-fluorouracil (5-FU). The study evaluated the cytotoxic effects of sildenafil, tezosentan and levosimendan alone and in combination with 5-FU on urological cancer cell lines... The findings suggest that levosimendan can be used in conjunction with 5-FU to reduce the required dose of 5-FU, thereby minimizing side effects without compromising therapeutic efficacy. This study offers a new perspective for enhancing therapeutic outcomes in patients with urological cancers."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urethral Cancer • Urology

Reactive oxygen species mitigate perturbations in coronary microvascular tone in exercising swine with multiple risk factors (ESC 2023) - "Despite elevated ET plasma levels in DM+HFD+CKD swine, combined ETA/ETB receptor blockade with tezosentan did not affect myocardial O2 balance in either Normal or DM+HFD+CKD swine (Fig C, D). In swine, 6 months exposure to multiple risk factors resulted in increased oxidative stress that paradoxically acted to mitigate perturbations in coronary microvascular tone via an H2O2-mediated coronary vasodilator influence. Despite an increase in circulating ET levels, we found no evidence for an increased ET-1 mediated coronary vasoconstrictor influence."

Clinical • Cardiovascular • Dyslipidemia • CAT

Repurposing of the Drug Tezosentan for Cancer Therapy. (PubMed, Curr Issues Mol Biol) - "This review intends to demonstrate the potential of this drug in the field of oncology. Drug repurposing can be an excellent way to improve the known profiles of first-line drugs and to solve several resistance problems of these same antineoplastic drugs."

Journal • Review • Cardiovascular • Hypertension • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • EDN1

Efficacy of pharmacologic therapies in patients with acute heart failure: A network meta-analysis. (PubMed, Front Pharmacol) - " After screening 14,888 citations, 23 RCTs (17,097 patients) were included, focusing on nesiritide, placebo, serelaxin, rhANP, omecamtiv mecarbil, tezosentan, KW-3902, conivaptan, tolvaptan, TRV027, chlorothiazide, metolazone, ularitide, relaxin, and rolofylline. No drug was superior to the other drugs for the secondary outcomes and safety outcomes. Current drugs for AHF show similar efficacy and safety."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system. (PubMed, J Biomed Sci) - "These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Pneumonia • Respiratory Diseases • Transplantation • CXCL8 • IL6

Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research. (PubMed, Int J Surg) - "It is suggested that NO-ASA, TS, and FLUR can be introduced as promising therapeutics to improve intestinal I/R injury."

Journal • Preclinical • Immunology • Inflammation • Reperfusion Injury • ICAM1 • IFNG • NFKB1

The protective effect of endothelin receptor antagonists against surgically induced impairment of gastrointestinal motility in rats. (PubMed, J Smooth Muscle Res) - "Furthermore, tezosentan alleviated the decrease in the contractile response of the longitudinal jejunal smooth muscle strips to carbachol in vitro induced by L+M. The serum ET(1-21) concentration was not increased in either the early or the late phase POI groups after surgery compared to control animals. This study indicates that delay in the intestinal transit in late phase of surgically induced POI involves an ET-dependent mechanism."

Journal • Gene Therapies • Ischemic stroke • Reperfusion Injury

Chronic hypoxia changes gene expression profile of primary rat carotid body cells: consequences on the expression of NOS isoforms and ET-1 receptors. (PubMed, Physiol Genomics) - "The treatment with Tezosentan (ET-1 receptor blocker) during CH up-regulated all three NOS isoforms, while the NOS blocker L-NAME induced up-regulation of iNOS and ET and down-regulated the protein levels of ET. These results showed that CH for 7 days changed the cultured cells CB gene expression profile, the NO and ET-1 signaling pathways were highly enriched and these two signaling pathways interfered on the protein expression of each other."

Journal

Target-Mediated Population Pharmacokinetic Modeling of Endothelin Receptor Antagonists. (PubMed, Pharm Res) - "The developed TMDD PK models are a next step towards understanding the complex PK of ERAs and further support the hypothesis that TMDD is a class effect of ERAs."

Clinical • Journal • PK/PD data