Last update 01 Nov 2024

ECE

Last update 01 Nov 2024

Basic Info

Synonyms

ECE, ECE-1, ECE1

+ [2]

Introduction

Converts big endothelin-1 to endothelin-1.

Drugs associated with ECE

CGS 34043

Target

ECE

Mechanism

ECE inhibitors

Active Org.

Novartis AG

Originator Org.

Novartis AG

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CGS 35066

Target

ECE

Mechanism

ECE inhibitors

Active Org.

Novartis AG

Originator Org.

Novartis AG

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SM-19712

Target

ECE

Mechanism

ECE inhibitors

Active Org.-

Originator Org.

Sumitomo Pharmaceuticals Co., Ltd.

Active Indication-

Inactive Indication

Renal Insufficiency [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ECE

NCT00885989 / CompletedPhase 1

A Placebo-Controlled, Combined Single and Multiple Rising Dose Study to Determine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SLV338 After Intravenous Administration in Healthy Male Subjects

This study will investigate the safety and tolerability of the first IV dosing of SLV338 in healthy volunteers.

Start Date01 May 2009

Sponsor / Collaborator

Solvay Pharmaceuticals, Inc.

NCT00735085 / TerminatedPhase 2

A Randomized, Double Blind, Placebo-Controlled Dose Escalation Study to Investigate the Safety and Pharmacokinetics After Single and Multiple Doses of SLV334 in Sequential Cohorts of Patients With Moderate and Severe Traumatic Brain Injury

A Randomized, Double Blind, Placebo Controlled, Phase 2 Dose Escalation Study to Investigate the Safety and Pharmacokinetics after Single and Multiple I.V. Doses of SLV334 in Sequential Cohorts of Patients with Moderate and Severe Traumatic Brain Injury.

Start Date01 Apr 2009

Sponsor / Collaborator

Abbott Products LLC

[+1]

EUCTR2004-000305-21-GB / Not yet recruitingPhase 2

A randomized, placebo-controlled, double-blind, six-arm, dose escalation, multi-center study to evaluate the efficacy and safety of SLV306: 150, 300, 600 mg once daily, 150-300 mg twice daily and amlodipine 5-10 mg once daily in subjects with hypertension

Start Date06 Sep 2006

Sponsor / Collaborator

Solvay Pharmaceuticals, Inc.

100 Clinical Results associated with ECE

100 Translational Medicine associated with ECE

0 Patents (Medical) associated with ECE

1,032

Literatures (Medical) associated with ECE

01 Dec 2024·Biofilm

Antifungal and antibiofilm activities of flavonoids against Candida albicans: Focus on 3,2'-dihydroxyflavone as a potential therapeutic agent.

Article

Author: Lee, Jintae ; Kim, Yong-Guy ; Park, Inji ; Lee, Jin-Hyung

Effective management of microbial biofilms holds significance within food and medical environments. Candida albicans, an opportunistic fungus, forms mucosal biofilms closely linked to candidiasis and drug-resistant infections due to their drug tolerance. Morphologic change from yeast to filamentous cells is a key virulence factor and a prerequisite for biofilm development. This study investigated the anti-fungal and antibiofilm activities of 20 flavonoids against C. albicans. With their known antioxidant capabilities, flavonoids hold promise in combating infections associated with biofilms. Among them, flavone and its derivatives exhibited moderate antifungal activity, 3,2'-dihydroxyflavone (3,2'-DHF) at 1 μg/mL exhibited strong antibiofilm activity (MIC 50 μg/mL). In addition, 3,2'-DHF dramatically inhibited cell aggregation and germ tube/hyphae formation. Transcriptomic analyses revealed that flavone and 3,2'-DHF behaved differently, as 3,2'-DHF downregulated the expressions of germ tube/hyphae-forming and biofilm-related genes (ECE1, HWP1, TEC1, and UME6) but upregulated the biofilm/hyphal regulators (CHK1, IFD6, UCF1, and YWP1). Tests evaluating toxicity with plant and nematode models revealed that flavone and 3,2'-DHF exhibited mild toxicity. Current results indicate that hydroxylated flavone derivatives can enhance anti-fungal and antibiofilm activities and provide a source of potential anti-fungal agents against drug-resistant C. albicans.

04 Sep 2024·Clinical Science

Endothelin-1 down-regulates nuclear factor erythroid 2-related factor-2 and contributes to perivascular adipose tissue dysfunction in obesity

Article

Author: Costa, Rafael M. ; Bruder-Nascimento, Thiago ; Pedersoli, Carina A. ; Alves, Juliano V. ; Oliveira-Neto, José Teles ; Lima, Anna Flavia R. ; Leiria, Luiz Osório S. ; Silva-Neto, Júlio A. ; Dias, Thiago B. ; Rodrigues, Daniel ; Tostes, Rita C. ; Bruder-Nascimento, Ariane ; Carneiro, Fernando S. ; Machado, Mirele R. ; Barros, Paula R. ; Bressan, Alecsander F. M. ; Garcia, Luis V.

AbstractPerivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg−1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3β and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.

14 Aug 2024·mBio

Variations in candidalysin amino acid sequence influence toxicity and host responses

Article

Author: Maufrais, Corinne ; Naglik, Julian R ; Hube, Bernhard ; Permal, Emmanuelle ; Priest, Emily L ; Sullivan, Derek ; Lee, Sejeong ; Lyon, Claire M ; d'Enfert, Christophe ; Richardson, Jonathan P ; Ryan, Adam P ; McManus, Brenda A ; Wickramasinghe, Don N ; Hepworth, Olivia W ; Butler, Geraldine

ABSTRACTCandida albicans causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in C. albicans strain SC5314, but recent investigations have revealed candidalysin “variants” of differing amino acid sequence in isolates of C. albicans , and the related species C. dubliniensis , and C tropicalis , suggesting that sequence variation among candidalysins may be widespread in natural populations of these Candida species. Here, we analyzed ECE1 gene sequences from 182 C . albicans isolates, 10 C . dubliniensis isolates, and 78 C . tropicalis isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant Candida species. IMPORTANCE Fungal infections are a significant burden to health. Candidalysin is a toxin produced by Candida albicans that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species C. dubliniensis and C. tropicalis , thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin “variant” toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of C. albicans , C. dubliniensis , and C. tropicalis and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity.

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ECE

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