Randomized, Double-blind, Placebo-controlled, Parallel Groups, Multicenter Pivotal Study Assessing the Efficacy and Safety of 15 mg Twice a Day (BID) of SER150 in Well-controlled Type 2 Diabetic Patients With Diabetic Kidney Disease and Albuminuria in Treatment With an Angiotensin Converting Enzyme Inhibitor or an Angiotensin Receptor Antagonist

This study is to assess the efficacy and safety of SER150 administered for 24 weeks as a 15 mg twice a day BID dose (except on Day 168 15 mg QD) in participants with type 2 diabetes (T2D) and albuminuria in treatment with either an angiotensin converting enzyme inhibitor (ACEi) or an angiotensin receptor antagonist (ARB).

Start Date18 Aug 2021

Sponsor / Collaborator

Serodus ASA

EUCTR2011-006207-36-DK / Unknown statusNot ApplicableIIT

A multi centre, double blind, randomised, placebo controlled crossover study to evaluate the efficacy and tolerability of picotamide in the prophylaxis of migraine in patients presenting with migraine with aura - PICOTAMIDE IN THE PROPHYLAXIS OF MIGRAINE WITH AURA

Start Date28 Mar 2012

Sponsor / Collaborator-

NCT01551381 / TerminatedPhase 2

Double-blind, Controlled Study in Healthy and Type 2 Diabetic Subjects to Assess Safety, Tolerability and Pharmacokinetics of 28 Days EV-077 Treatment, and the Effects on Platelet Function, Vascular Inflammation and Oxidative Stress.

The principal objective of this study is to evaluate the safety and tolerability of repeated doses of EV-077-3201-2TBS given to diabetic subjects over a 4 week treatment period. The secondary aim of this initial Phase IIa study is to evaluate the effect of multiple oral doses of EV-077-3201-2TBS on platelet function, vascular function, vascular inflammation, vascular oxidative stress, renal function and a selection of exploratory parameters and biomarkers in type 2 diabetic subjects, as well as multiple dose pharmacokinetics in diabetic subjects.
In order to ensure the safety of the diabetic subjects, initial parts of the study will evaluate the safety and tolerability of EV-077-3201-2TBS. In Part A, the safety of different doses EV-077-3201-2TBS will be investigated in healthy subjects treated for 4 weeks. In parallel, Part B will investigate potential interactions between EV-077-3201-2TBS and ASA in healthy subjects. Part C will then investigate the safety, pharmacokinetics and pharmacodynamics of EV-077-3201-2TBS in type 2 diabetic subjects with and without concomitant ASA therapy.

Start Date01 Jan 2012

Sponsor / Collaborator

Evolva SA

100 Clinical Results associated with TBXA2R x TXA2 synthase

100 Translational Medicine associated with TBXA2R x TXA2 synthase

0 Patents (Medical) associated with TBXA2R x TXA2 synthase

Literatures (Medical) associated with TBXA2R x TXA2 synthase

01 Sep 2022·American Journal of Respiratory and Critical Care Medicine

Thromboxane–Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis

Article

Author: Kropski, Jonathan A. ; Gutor, Sergey ; Han, Wei ; Banovich, Nicholas E. ; Tada, Yuji ; Blackwell, Timothy S. ; Gokey, Jason J. ; Polosukhin, Vasiliy V. ; Winters, Nichelle I. ; Freeman, Michael L. ; Camarata, Jane E. ; Sherrill, Taylor P. ; Young, Lisa R. ; Sabusap, Carleen ; West, James D. ; Carrier, Erica J. ; Chen, Jingyuan ; Tanjore, Harikrishna ; Chen, Xinping ; Suzuki, Toshio ; Rathinasabapathy, Anandharajan ; Gulleman, Peter

Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objectives: On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We used TBXA2R-deficient mice and small-molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. Measurements and Main Results: TBXA2R expression was upregulated in fibroblasts in the lungs of patients with IPF and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting that an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes, which are nonenzymatic products of arachidonic acid induced by reactive oxygen species, were persistently elevated during fibrosis. F2-isoprostanes induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-β (transforming growth factor-β) signaling. In vivo treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.

01 Apr 2021·British Journal of DermatologyQ1 · MEDICINE

An additional drug repurposing study for hidradenitis suppurativa/acne inversa

Q1 · MEDICINE

Letter

Author: Readhead, B. ; Dudley, J.T. ; Zouboulis, C.C.

Current transcriptome and proteome studies have identified differentially regulated genes and proteins in hidradenitis suppurativa/acne inversa (HS), both in entire involved skin and in involved skin apocrine glands.In this report, we provide addnl. information obtained by further anal. of our data using mol. drug information available through chemogenomic studies.Raw microarray profiles from our own previous studies downloaded from Gene Expression Omnibus (GSE137141) and (GSE144801) were used in this study.The data for anal. originated from whole lesional skin (LS) and nonlesional skin (NLS) of 28 European patients [20 female, eight male; aged 35.0 (10.2) years] with active HS Hurley stage II-III and healthy skin (CS) of 12 matched controls [aged 37.1 (13.2) years].The comparison of LS vs. NLS revealed several new drug target genes, namely ABAT, ADH1C, ADIRF, ADRA1A, ANDR, CFD, CHRM1, CLEC3B, CP3A4, DACB, DRD1, DRD5, GABBR1, GBP6, GBRA6, GBRR1, GCR, GPD1, GRIA1, GRM4, HRH1, IF4H, KRT6B, LPA, MCR, MRCA, MRCB, OPRD, OPRM, PA24A, PBPC, PLAT, PLG, PRKAB1, PTGS1, PTGS2, RPL38, SLC6A4, TA2R, TBXA2R, THAS, TLR2 and UTS2, in addition to the ones detected as HS biomarkers in our previous study, namely DEFB4A/ DEFB4B, GJB2, KRT6A, KRT16, MMP1, MMP9, PI3, S100A7A, S100A8, S100A9, S100A12, SERPINB3, SERPINB4 and SPRR3.Therefore, repurposing drugs may become future targets of investigator-initiated studies supported from peer-reviewed public funding sources.

01 Feb 2020·Thrombosis and HaemostasisQ2 · MEDICINE

Retracted Article: Thromboxane A2 Synthase and Thromboxane Receptor Deletion Reduces Ischaemia/Reperfusion-Evoked Inflammation, Apoptosis, Autophagy and Pyroptosis

Q2 · MEDICINE

Article

Author: Chen, Kuo-Hsin ; Chien, Chiang-Ting ; Cheng, Yu-Hsiuan ; Chueh, Tsung-Hung

Abstract Aim Enhancement of thromboxane A2 (TXA2) synthase (TXAS) activity, TXA2 release, and thromboxane prostanoid (TP) receptor activation leads to vasoconstriction and oxidative injury. We explored whether genetic deletion of TXAS/TXA2/TP signalling may reduce renal ischaemia/reperfusion (I/R) injury in mice. Materials and Methods Renal haemodynamics and function were evaluated in TXAS+/+TP+/+ (wild-type, WT), TXAS−/− (TXS−/−), TP−/− and TXAS−/−TP−/− (double knockout, dKO) mice in response to intravenous TXA2 mimetic-U46619 and 45-minute renal ischaemia and 4-hour reperfusion injury. We examined renal TXAS and TP expression, blood urea nitrogen (BUN) and creatinine, reactive oxygen species (ROS) amount, pro-inflammatory cytokines and pathophysiologic mechanisms, including apoptosis, autophagy and pyroptosis under I/R injury. Results Renal I/R enhanced the levels of TXAS, TP, nuclear factor-κB, nicotinamide adenine dinucleotide phosphate oxidase gp91, Bax/Bcl-2/caspase-3/apoptosis, Beclin-1/LC3-II/autophagy, caspase-1/gasdermin D/interleukin-1β/pyroptosis, renal thromboxane B2 (TXB2) concentration, ROS amount, plasma BUN, creatinine and TXB2 and decreased renal endothelial nitric oxide synthase expression in WT mice. All these enhanced parameters were significantly decreased in three KO mice. Intravenous U46619 significantly decreased renal microcirculation and enhanced gp91 and Bax/Bcl-2 in WT and TXS−/− but not TP−/− in dKO mice. I/R significantly decreased renal microcirculation in all mice; however, the time for recovery to baseline renal blood flow level was significantly shortened in TXS−/−, TP−/−and dKO mice versus WT mice. Blockade of TXAS/TP signalling attenuated I/R-enhanced pro-inflammatory cytokine profile. Conclusion Blockade of TXAS/TXA2/TP signalling confers renal protection against I/R injury through the actions of anti-oxidation, anti-inflammation, anti-apoptosis, anti-autophagy and anti-pyroptosis.

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