Delving into the Latest Updates on Ilepatril with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ACE x CD10

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

Molecular FormulaC22H28N2O5S

InChIKeyFXKFFTMLFPWYFH-RDGPPVDQSA-N

CAS Registry473289-62-2

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.

07 Dec 2012·Investigative Opthalmology & Visual ScienceQ2 · MEDICINE

Early Loss of Innervation of Cornea Epithelium in Streptozotocin-Induced Type 1 Diabetic Rats: Improvement with Ilepatril Treatment

Q2 · MEDICINE

ArticleOA

Author: Eric P. Davidson ; Lawrence J. Coppey ; Mark A. Yorek

PURPOSECornea confocal microscopy is emerging as a clinical tool to evaluate the development and progression of diabetic neuropathy. The purpose of these studies was to characterize the early changes in corneal sensitivity and innervation in a rat model of type 1 diabetes in relation to standard peripheral neuropathy endpoints and to assess the effect of Ilepatril, a vasopeptidase inhibitor which blocks angiotensin converting enzyme and neutral endopeptidase, on these endpoints.METHODSStreptozotocin-diabetic rats 8 weeks duration were treated with or without Ilepatril for the last 6 weeks of the experimental period. Afterwards, standard diabetic neuropathy endpoints, subbasal corneal nerves and innervation of the epithelium, corneal sensitivity using a Cochet-Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery were examined.RESULTSDiabetes caused a decrease in nerve conduction velocity, thermal hypoalgesia, and a reduction in intraepidermal nerve fiber profiles. In the cornea there was a decrease in corneal nerve fibers innervating the epithelium and corneal sensitivity, but subbasal corneal nerve fibers was not changed. Vascular relaxation in response to acetylcholine was decreased in the posterior ciliary artery. These defects were partially to completely prevented by Ilepatril treatment.CONCLUSIONSThese studies suggest that in type 1 diabetic rats decreased innervation of the cornea epithelium occurs early in diabetes and prior to a detectable decrease in subbasal corneal nerves and that these and other diabetic neuropathy-related defects can be partially to completely prevented by a vasopeptidase inhibitor.

01 Feb 2012·European Journal of PharmacologyQ3 · MEDICINE

Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats

Q3 · MEDICINE

Article

Author: Amey Holmes ; Mark A. Yorek ; Lawrence J. Coppey ; Eric P. Davidson

Treating high fat fed/low dose streptozotocin-diabetic rats; model of type 2 diabetes, with ilepatril (vasopeptidase inhibitor, blocks neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE)) improved vascular and neural functions. Next, studies were performed to determine the individual effect of inhibition of NEP and ACE on diabetes-induced vascular and neural dysfunctions. High fat fed rats (8 weeks) were treated with 30 mg/kg streptozotocin (i.p.) and after 4 additional weeks, were treated for 12 weeks with ilepatril, enalapril (ACE inhibitor) or candoxatril (NEP inhibitor) followed by analysis of vascular and neural functions. Glucose clearance was impaired in diabetic rats and was not improved with treatment although treatment with ilepatril or candoxatril partially improved insulin stimulated glucose uptake by isolated soleus muscle. Diabetes caused slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber (IENF) profiles and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide (CGRP) in epineurial arterioles of the sciatic nerve. Inhibition of NEP improved nerve conduction velocity and inhibition of NEP or ACE improved thermal sensitivity and protected IENF density. Ilepatril and candoxatril treatments of diabetic rats were efficacious in improving vascular responsiveness to acetylcholine in epineurial arterioles; whereas all three treatments improved vascular response to CGRP. These studies suggest that inhibition of NEP and ACE activity is an effective approach for treatment of type 2 diabetes neural and vascular complications.

100 Deals associated with Ilepatril

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06604

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 3	RU	Sanofi	01 Dec 2005
Hypertension	Phase 3	TW	Sanofi SA	01 Dec 2005
Hypertension	Phase 3	BR	Sanofi	01 Dec 2005
Hypertension	Phase 3	CN	Sanofi	01 Dec 2005
Hypertension	Phase 3	NL	Sanofi	01 Dec 2005
Hypertension	Phase 3	PT	Sanofi	01 Dec 2005
Hypertension	Phase 3	GR	Sanofi	01 Dec 2005
Hypertension	Phase 3	IT	Sanofi	01 Dec 2005
Hypertension	Phase 3	SG	Sanofi	01 Dec 2005
Hypertension	Phase 3	PL	Sanofi	01 Dec 2005