Delving into the Latest Updates on Ilepatril with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ACE x CD10

Action

inhibitors

Mechanism

ACE inhibitors(Angiotensin-converting enzyme inhibitors), enkephalinase inhibitors(Neprilysin inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseUrogenital Diseases

Active Indication-

Inactive Indication

Diabetic NephropathiesHeart FailureHypertension

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Hoechst Pakistan Ltd.

Sanofi

Sanofi SA

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H28N2O5S

InChIKeyFXKFFTMLFPWYFH-RDGPPVDQSA-N

CAS Registry473289-62-2

The primary objective is to assess the antihypertensive efficacy of 4 different AVE 7688 doses on the change from baseline in trough diastolic blood pressure at the end of week 12.
The secondary objectives are:
To assess the antihypertensive efficacy of 4 different AVE 7688 doses on the change from baseline in trough systolic blood pressure at the end of week 12
To compare the percentages of responders after 12 week of treatment
To evaluate the long term safety and tolerability of AVE 7688 with particular attention to angioedema

Start Date01 Dec 2005

Sponsor / Collaborator

Sanofi SA

100 Clinical Results associated with Ilepatril

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100 Translational Medicine associated with Ilepatril

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100 Patents (Medical) associated with Ilepatril

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41

Literatures (Medical) associated with Ilepatril

01 May 2016·The Journal of Pharmacology and Experimental TherapeuticsQ3 · MEDICINE

Pharmacologic Comparison of Clinical Neutral Endopeptidase Inhibitors in a Rat Model of Acute Secretory Diarrhea

Q3 · MEDICINE

Article

Author: Neckermann, Georg ; Arnett, Stacy D ; Ji, Yuhua ; Oliva, Jonathan ; Campbell, Mary A ; Tajfirouz, Deena ; Ruminski, Peter G ; Meyers, Marvin J ; Choy, Robert K M ; de Hostos, Eugenio ; Bond, Brian R ; Yu, Ying ; Prinsen, Michael J ; Griggs, David W

Racecadotril (acetorphan) is a neutral endopeptidase (NEP) inhibitor with known antidiarrheal activity in animals and humans; however, in humans, it suffers from shortcomings that might be improved with newer drugs in this class that have progressed to the clinic for nonenteric disease indications. To identify potentially superior NEP inhibitors with immediate clinical utility for diarrhea treatment, we compared their efficacy and pharmacologic properties in a rat intestinal hypersecretion model. Racecadotril and seven other clinical-stage inhibitors of NEP were obtained or synthesized. Enzyme potency and specificity were compared using purified peptidases. Compounds were orally administered to rats before administration of castor oil to induce diarrhea. Stool weight was recorded over 4 hours. To assess other pharmacologic properties, select compounds were orally administered to normal or castor oil-treated rats, blood and tissue samples collected at multiple time points, and active compound concentrations determined by mass spectroscopy. NEP enzyme activity was measured in tissue homogenates. Three previously untested clinical NEP inhibitors delayed diarrhea onset and reduced total stool output, with little or no effect on intestinal motility assessed by the charcoal meal test. Each was shown to be a potent, highly specific inhibitor of NEP. Each exhibited greater suppression of NEP activity in intestinal and nonintestinal tissues than did racecadotril and sustained this inhibition longer. These results suggest that newer clinical-stage NEP inhibitors originally developed for other indications may be directly repositioned for treatment of acute secretory diarrhea and offer advantages over racecadotril, such as less frequent dosing and potentially improved efficacy.

02 Jan 2015·Clinical and Experimental HypertensionQ4 · MEDICINE

Cardiorenal protection in experimental hypertension with renal failure: comparison between vasopeptidase inhibition and angiotensin receptor blockade

Q4 · MEDICINE

Article

Author: Holleck-Weithmann, Sven ; Kreutz, Reinhold ; Halleck, Fabian ; Rothermund, Lars ; Kossmehl, Peter ; Schröder, Katharina

OBJECTIVEThe aim of the present study was to compare the preventive impact of treatment with a vasopeptidase inhibitor (VPI) with an angiotensin-receptor blocker (ARB) on left ventricular (LV) function and renal damage in rats with renal failure after 5/6 renal ablation (Nx).METHODSRats (n = 15-20, each group) underwent either sham-operation (Sham) or 5/6 renal ablation (Nx). Two additional groups of Nx-animals (groups Nx-VPI and Nx-ARB) were treated with the VPI ilepatril (AVE7688, 30 mg kg(-1) d(-1)) or with the ARB olmesartan (10 mg kg(-1 )d(-1)). Animals were followed for 4 weeks.RESULTSSystolic blood pressure (SBP), LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) were increased 4 weeks after Nx (p < 0.05). LV pressure rise (+dP/dt/LVPmax), LV pressure fall (-dP/dt/LVPmax), and creatinine clearance decreased, while albuminuria and renal glomerulosclerosis index (GSI) increased with Nx (p < 0.05, respectively). In comparison to Nx, treatment with both VPI and ARB normalized SBP, LVH, LVEDP, +dP/dt/LVPmax, and -dP/dt/LVPmax to Sham control levels. GSI, but not creatinine clearance, was also normalized in response to both treatments. The significant increase in albuminuria observed in Nx (+230-fold versus Sham, p < 0.0001) was partially reduced in Nx-VPI (+47-fold versus Sham, p < 0.0001) and fully abolished in Nx-ARB.CONCLUSIONSBoth ilepatril and olmesartan conferred strong cardiorenal protective effects in rats with renal failure. While cardioprotection was clearly comparable with both treatment regimens, the ARB provided a better protection against the increase in albuminuria, although renal function and structural kidney changes were similarly affected by the VIP and ARB.

05 Aug 2014·Environmental Science & TechnologyQ1 · ENVIRONMENTAL SCIENCE & ECOLOGY

Predictive Endocrine Testing in the 21st Century Usingin VitroAssays of Estrogen Receptor Signaling Responses

Q1 · ENVIRONMENTAL SCIENCE & ECOLOGY

Article

Author: Knudsen, Thomas B. ; Filer, Dayne L. ; Martin, Matt T. ; Xia, Menghang ; Huang, Ruili ; Sipes, Nisha S. ; Rotroff, Daniel M. ; Houck, Keith A. ; Reif, David M. ; Dix, David J. ; Judson, Richard S.

Thousands of environmental chemicals are subject to regulatory review for their potential to be endocrine disruptors (ED). In vitro high-throughput screening (HTS) assays have emerged as a potential tool for prioritizing chemicals for ED-related whole-animal tests. In this study, 1814 chemicals including pesticide active and inert ingredients, industrial chemicals, food additives, and pharmaceuticals were evaluated in a panel of 13 in vitro HTS assays. The panel of in vitro assays interrogated multiple end points related to estrogen receptor (ER) signaling, namely binding, agonist, antagonist, and cell growth responses. The results from the in vitro assays were used to create an ER Interaction Score. For 36 reference chemicals, an ER Interaction Score >0 showed 100% sensitivity and 87.5% specificity for classifying potential ER activity. The magnitude of the ER Interaction Score was significantly related to the potency classification of the reference chemicals (p < 0.0001). ERα/ERβ selectivity was also evaluated, but relatively few chemicals showed significant selectivity for a specific isoform. When applied to a broader set of chemicals with in vivo uterotrophic data, the ER Interaction Scores showed 91% sensitivity and 65% specificity. Overall, this study provides a novel method for combining in vitro concentration response data from multiple assays and, when applied to a large set of ER data, accurately predicted estrogenic responses and demonstrated its utility for chemical prioritization.

100 Deals associated with Ilepatril

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 3	Russia	Sanofi	01 Dec 2005
Hypertension	Phase 3	Taiwan Province	Sanofi SA	01 Dec 2005
Hypertension	Phase 3	South Africa	Sanofi	01 Dec 2005
Hypertension	Phase 3	Netherlands	Sanofi	01 Dec 2005
Hypertension	Phase 3	Greece	Sanofi	01 Dec 2005
Hypertension	Phase 3	Hong Kong	Sanofi SA	01 Dec 2005
Hypertension	Phase 3	Germany	Sanofi	01 Dec 2005
Hypertension	Phase 3	Argentina	Sanofi	01 Dec 2005
Hypertension	Phase 3	Spain	Sanofi	01 Dec 2005
Hypertension	Phase 3	Malaysia	Sanofi	01 Dec 2005