Delving into the Latest Updates on EV-077 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [7]

Target

TBXA1R x TBXA2R x TXA2 synthase

Action

antagonists, inhibitors

Mechanism

TBXA1R antagonists(thromboxane A1 receptor antagonists), TBXA2R antagonists(Thromboxane A2 receptor antagonists), TXA2 synthase inhibitors(Thromboxane A2 synthase inhibitors)

Therapeutic Areas

Endocrinology and Metabolic DiseaseUrogenital Diseases

Active Indication

AlbuminuriaDiabetes Mellitus, Type 2Diabetic Nephropathies

Inactive Indication

Diabetes Mellitus, Noninsulin-Dependent, 2Influenza A virus infectionstress oxidative+ [1]

Originator Organization

Evolva Holding SA

Active Organization

Serodus ASA

Evolva Holding SA

Inactive Organization

Evolva SA

Drug Highest PhasePhase 2/3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H23ClO5

InChIKeyWHUIENZXNGAHQI-GKZDNZBASA-N

CAS Registry1041850-31-0

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

EUCTR2014-003985-25-DE

/ Not yet recruitingPhase 2

Multi-centre, randomized, double-blind, placebo-controlled, phase II study assessing in two sequential cohorts the safety, efficacy and tolerability of a 15 mg BID and a 30 mg BID doses of SER150TBS in well controlled type II diabetic patients with diabetic nephropathy and albuminuria in stable antidiabetic treatment

Start Date12 Jun 2015

Sponsor / Collaborator

Serodus ASA

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 EV-077

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100 Translational Medicine associated with EV-077

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100 Patents (Medical) associated with EV-077

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11

Literatures (Medical) associated with EV-077

07 Mar 2023·Biochemistry

Phosphorylation-Competent Metastable State of Escherichia coli Toxin HipA

Article

Author: Sinha, Krishnendu ; Basu, Gautam ; Dev, Aditya ; Polley, Smarajit ; Chakrabarty, Suman ; Ganguly, Himal K. ; Pandey, Bhawna

Phosphorylation is a key post-translational modification that alters the functional state of many proteins. The Escherichia coli toxin HipA, which phosphorylates glutamyl-tRNA synthetase and triggers bacterial persistence under stress, becomes inactivated upon autophosphorylation of Ser150. Interestingly, Ser150 is phosphorylation-incompetent in the crystal structure of HipA since it is deeply buried ("in-state"), although in the phosphorylated state it is solvent exposed ("out-state"). To be phosphorylated, a minor population of HipA must exist in the phosphorylation-competent "out-state" (solvent-exposed Ser150), not detected in the crystal structure of unphosphorylated HipA. Here we report a molten-globule-like intermediate of HipA at low urea (∼4 kcal/mol unstable than natively folded HipA). The intermediate is aggregation-prone, consistent with a solvent exposed Ser150 and its two flanking hydrophobic neighbors (Val/Ile) in the "out-state". Molecular dynamics simulations showed the HipA "in-out" pathway to contain multiple free energy minima with an increasing degree of Ser150 solvent exposure with the free energy difference between the "in-state" and the metastable exposed state(s) to be ∼2-2.5 kcal/mol, with unique sets of hydrogen bonds and salt bridges associated with the metastable loop conformations. Together, the data clearly identify the existence of a phosphorylation-competent metastable state of HipA. Our results not only suggest a mechanism of HipA autophosphorylation but also add to a number of recent reports on unrelated protein systems where the common proposed mechanism for phosphorylation of buried residues is their transient exposure even without phosphorylation.

01 Oct 2022·Environmental Science and Pollution Research

Investigating the role of different maize (Zea mays L.) cultivars by studying morpho-physiological attributes in chromium-stressed environment

Article

Author: Hassan, Amara ; Rasheed, Rizwan ; Parveen, Abida ; Hussain, Iqbal ; Hussain, Saddam

Because of global land surface warming, heavy metal toxicity is expected to occur more often and more intensely, affecting the growth and development of the major cereal crops such as maize (Zea mays L.) in several ways, thus affecting the production component of food security. Hence, it is important to know the best cultivars of Z. mays in abiotic stress environment to fulfill the market demand of this staple food. For this purpose, we investigate the present study to find the best Z. mays cultivar to be grown in chromium (Cr)-contaminated sand (200 µM). In this experiment, we have studied 10 cultivars (Malka, Sadaf, Pearl, CZP, YY, YH, MMRI-yellow, Sahiwal, EV-20, and EV-77) of Z. mays grown in plastic pots for 4 weeks (in addition with seed germination) under Cr - (0 µM) and Cr + (200 µM) in sand medium. Based on the findings of the current experiment, we illustrated that Cr toxicity induced a significant (P < 0.05) reduction in shoot length, root length, shoot fresh weight, root fresh weight, shoot dry weight and root dry weight, chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid content and induced oxidative damage to membrane-bounded organelles by increasing the malondialdehyde and hydrogen peroxide which were manifested by flavonoid and phenolic contents. Moreover, Cr uptake was also higher in the plants grown in the Cr-contaminated sand compared to the plants grown without the Cr-contaminated sand. We also noticed that Pearl, CZP, and Sahiwal cultivars are suggested to be Cr-tolerant cultivars as showed better growth and development in Cr-contaminated sand while Sadaf, MMRI, and EV-77 showed lower growth and composition in Cr-contaminated sand. The overall pattern of Z. mays cultivars grown in Cr-contaminated sand is as follows: Pearl > CZP > Sahiwal > YY > YH > EV-20 > Malka > EV-77 > MMRI-yellow > Sadaf. Conclusively, it can be identified that when grown in Cr-contaminated sand, Pearl, CZP, and Sahiwal have greater ability to grow in polluted soils. Overall, Z. mays cultivars showed better growth in Cr-stressed environment due to defense mechanism but further experiments needed to be conducted on molecular level.

02 Sep 2016·Current Pharmaceutical DesignQ4 · MEDICINE

Novel Anti-Platelets in Stable Coronary Artery Disease

Q4 · MEDICINE

Review

Author: Zacharia, Effimia ; Siasos, Gerasimos ; Rehal, Onkar ; Tousoulis, Dimitris ; Ioannou, Adam ; Papageorgiou, Nikolaos ; Zacharias, Konstantinos

BACKGROUNDApart from the acute thrombotic complications that lead to acute coronary syndromes (ACS), platelet activation also plays an important role in the initiation and progression of atherosclerosis. In addition, it is speculated that anti-platelet therapy can be beneficial for patients with stable coronary artery disease (CAD). Of note, patients on optimal anti-platelet treatment still experience thrombotic events, whereas complications, such as bleeding, cannot be ignored. In this light, novel antiplatelet regimens have been used to minimize the residual platelet activation without compromising normal haemostasis.METHODSWe performed a thorough search of the literature in order to review the beneficial role of novel antiplatelets in patients with stable CAD. We have also focused on studies that examine the effect of these drugs on platelet reactivity as well as on cardiovascular outcomes.CONCLUSIONSpecific agents, such as vorapaxar and cilostazol, have been found to reduce platelet reactivity as well as to improve patients' prognosis. Of note, the use of novel antiplatelets is of clinical importance in patients with increased thrombotic status and in those with resistance to classic antiplatelets. However, the available data on most of the novel antiplatelets are mainly derived from studies including ACS patients undergoing angioplasty Therefore, large randomized controlled studies are required to evaluate the clinical benefit of novel antiplatelets in patients with stable CAD.

100 Deals associated with EV-077

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Albuminuria	Phase 3	New Zealand	Serodus ASA	18 Aug 2021
Albuminuria	Phase 3	Australia	Serodus ASA	18 Aug 2021
Diabetes Mellitus, Type 2	Phase 3	Australia	Serodus ASA	18 Aug 2021
Diabetes Mellitus, Type 2	Phase 3	New Zealand	Serodus ASA	18 Aug 2021
Diabetic Nephropathies	Phase 3	New Zealand	Serodus ASA	18 Aug 2021
Diabetic Nephropathies	Phase 3	Australia	Serodus ASA	18 Aug 2021
Diabetes Mellitus, Noninsulin-Dependent, 2	Preclinical	Germany	Evolva SA	01 Jan 2012
stress oxidative	Preclinical	Germany	Evolva SA	01 Jan 2012
Vasculitis	Preclinical	Germany	Evolva SA	01 Jan 2012
Influenza A virus infection	Preclinical	Switzerland	Evolva Holding SA	-