Delving into the Latest Updates on Daglutril with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CD10 x ECE

Action

inhibitors

Mechanism

ECE inhibitors(Endothelin-converting enzyme 1 inhibitors), enkephalinase inhibitors(Neprilysin inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseRespiratory Diseases+ [2]

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2Heart FailureHypertension+ [2]

Originator Organization

AbbVie, Inc.

Active Organization-

Inactive Organization

Solvay Pharmaceuticals, Inc.

AbbVie, Inc.AbbVie AS

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H38N2O6

InChIKeyXMQODGUTLZXUGZ-RPBOFIJWSA-N

CAS Registry182821-27-8

Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 μm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 μm), CNP and VIP (0.1 nm - 1 μm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10 μm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.

01 Dec 2016·AndrologiaQ4 · MEDICINE

Effects of endopeptidase inhibition on the relaxation response of isolated human penile erectile tissue to vasoactive peptides

Q4 · MEDICINE

Article

Author: Sonnenberg, J. E. ; Reichelt, K. ; Ückert, S. ; Kuczyk, M. A. ; Sohn, M. ; Rahardjo, H. E.

Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1 nm-1 μm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10 μm, for 20 min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides.

13 Oct 2015·Expert Opinion on PharmacotherapyQ3 · MEDICINE

An update of the blockade of the renin angiotensin aldosterone system in clinical practice

Q3 · MEDICINE

Review

Author: Márquez, Diego F ; Segura, Julián ; Ruilope, Luis M ; Ruiz-Hurtado, Gema

INTRODUCTIONCardiovascular disease (CVD) is the leading cause of death worldwide. Blockade of this system is commonly used in the treatment of cardiovascular (CV) and renal disease.AREAS COVEREDData from multiple clinical trials have provided good evidence about the benefit of blocking the system as a therapeutic target to reduce CV and renal events. We have reviewed all the tested combinations of different drugs counteracting the effects of the renin-angiotensin-aldosterone system.EXPERT OPINIONMonotherapy with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) remains valid in all the guidelines, whereas their dual combination has been discarded due to the absence of proven benefits in high CV risk patients and in patients with chronic kidney disease (CKD). The combination of the standard therapy with an ACEi or an ARB with a mineralocorticoid receptor blocker is a valid option, but has the inconvenience of frequent hyperkalemia in patients with CKD. Similarly, the addition of the direct renin inhibitor, aliskiren, to this standard therapy is not particularly supported in diabetic patients. New dual-acting blockers, for example, those combining valsartan and neprilysin inhibitors (LCZ696-Novartis) or endothelin converting enzyme inhibitors and neprilysin inhibitors (ECEI, Daglutril-Solvay), are currently under investigation.

100 Deals associated with Daglutril

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05796

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	Italy	Solvay Pharmaceuticals, Inc.	01 Jul 2005
Kidney Diseases	Phase 2	Italy	Solvay Pharmaceuticals, Inc.	01 Jul 2005
Heart Failure	Phase 2	-	AbbVie, Inc.	-
Heart Failure	Phase 2	Germany	AbbVie AS	-
Heart Failure	Phase 2	United States	AbbVie AS	-
Hypertension	Phase 2	United States	AbbVie AS	-
Hypertension	Phase 2	European Union	AbbVie AS	-
Pulmonary Arterial Hypertension	Phase 2	-	AbbVie, Inc.	-