Delving into the Latest Updates on Ataciguat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

sGC

Mechanism

sGC stimulants(Soluble guanylate cyclase stimulants)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Aortic Valve StenosisAortic Valve, Calcification OfIntermittent Claudication+ [2]

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Sanofi

Sanofi SA

Mayo Clinic

+ [2]

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H19Cl2N3O6S3

InChIKeyPQHLRGARXNPFCF-UHFFFAOYSA-N

CAS Registry254877-67-3

The primary objective of the current study is to determine whether Ataciguat (HMR1766) slows progression of valve calcification in patients with moderate calcific aortic valve stenosis. Secondary and tertiary objectives are to determine whether Ataciguat slows progression of aortic valve function, reduces systemic inflammation, and prevents left ventricular dysfunction in patients with moderate calcific aortic valve stenosis.

Start Date01 Jun 2015

Sponsor / Collaborator

Mayo Clinic

[+2]

NCT02049203 / CompletedPhase 1IIT

A Phase Ib Randomized, Placebo-controlled, Double-blinded Study Evaluating the Safety of Ataciguat (HMR1766) in Patients With Moderate Calcific Aortic Valve Stenosis

This study will determine whether Ataciguat (HMR1766) is well-tolerated in patients with mild to moderate calcific aortic valve stenosis. The primary focus of these studies will be on changes in blood pressure and orthostatic tolerance (i.e., ability to stand up without passing out), and determining whether treatment with Ataciguat results in significant reductions in blood pressure in this patient population.

Start Date01 Jan 2014

Sponsor / Collaborator

Mayo Clinic

[+3]

NCT00799656 / CompletedPhase 2

Efficacy and Safety of Oral Ataciguat (HMR1766) 200 mg Administered Once Daily for 28 Days on Pain Reduction in Patients With Neuropathic Pain. A Randomized, Double-blind, Placebo-controlled, Cross-over Study

The primary objective of this study is to assess the efficacy of ataciguat versus placebo in reducing pain intensity in patients with neuropathic pain.
The secondary objective is to assess the safety and tolerability of ataciguat versus placebo.

Start Date01 Nov 2008

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Ataciguat

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100 Translational Medicine associated with Ataciguat

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100 Patents (Medical) associated with Ataciguat

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25

Literatures (Medical) associated with Ataciguat

13 May 2021·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042)

Q1 · MEDICINE

Article

Author: Lang, Dieter ; Schlemmer, Karl-Heinz ; Gerisch, Michael ; Mittendorf, Joachim ; Schomber, Tibor ; El Sheikh, Sherif ; Becker-Pelster, Eva-Maria ; Benardeau, Agnes ; Wunder, Frank ; Mondritzki, Thomas ; Eitner, Frank ; Truebel, Hubert ; Dietz, Lisa ; Sandner, Peter ; Kern, Armin ; van den Akker, Focco ; Geiss, Volker ; Tinel, Hanna ; Hueser, Joerg ; Lampe, Thomas ; Stasch, Johannes-Peter ; Hahn, Michael G. ; Woltering, Elisabeth ; Knorr, Andreas ; Griebenow, Nils ; Kumar, Vijay ; Schaefer, Martina

Herein we describe the discovery, mode of action, and preclinical characterization of the soluble guanylate cyclase (sGC) activator runcaciguat. The sGC enzyme, via the formation of cyclic guanosine monophoshphate, is a key regulator of body and tissue homeostasis. sGC activators with their unique mode of action are activating the oxidized and heme-free and therefore NO-unresponsive form of sGC, which is formed under oxidative stress. The first generation of sGC activators like cinaciguat or ataciguat exhibited limitations and were discontinued. We overcame limitations of first-generation sGC activators and identified a new chemical class via high-throughput screening. The investigation of the structure-activity relationship allowed to improve potency and multiple solubility, permeability, metabolism, and drug-drug interactions parameters. This program resulted in the discovery of the oral sGC activator runcaciguat (compound 45, BAY 1101042). Runcaciguat is currently investigated in clinical phase 2 studies for the treatment of patients with chronic kidney disease and nonproliferative diabetic retinopathy.

01 May 2015·British Journal of PharmacologyQ2 · MEDICINE

The fibrate gemfibrozil is a NO‐ and haem‐independent activator of soluble guanylyl cyclase: in vitro studies

Q2 · MEDICINE

Article

Author: Martin, E ; Rukoyatkina, N ; Sobolevsky, M ; Papakyriakou, A ; Sharina, I G ; Spyroulias, G A ; Gambaryan, S

Background and PurposeFibrates are a class of drugs widely used to treat dyslipidaemias. They regulate lipid metabolism and act as PPARα agonists. Clinical trials demonstrate that besides changes in lipid profiles, fibrates decrease the incidence of cardiovascular events, with gemfibrozil exhibiting the most pronounced benefit. This study aims to characterize the effect of gemfibrozil on the activity and function of soluble guanylyl cyclase (sGC), the key mediator of NO signalling.Experimental ApproachHigh‐throughput screening of a drug library identified gemfibrozil as a direct sGC activator. Activation of sGC is unique to gemfibrozil and is not shared by other fibrates.Key ResultsGemfibrozil activated purified sGC, induced endothelium‐independent relaxation of aortic rings and inhibited platelet aggregation. Gemfibrozil‐dependent activation was absent when the sGC haem domain was deleted, but was significantly enhanced when sGC haem was lacking or oxidized. Oxidation of sGC haem enhanced the vasoactive and anti‐platelet effects of gemfibrozil. Gemfibrozil competed with the haem‐independent sGC activators ataciguat and cinaciguat. Computational modelling predicted that gemfibrozil occupies the space of the haem group and interacts with residues crucial for haem stabilization. This is consistent with structure‐activity data which revealed an absolute requirement for gemfibrozil's carboxyl group.Conclusions and ImplicationsThese data suggest that in addition to altered lipid and lipoprotein state, the cardiovascular preventive benefits of gemfibrozil may derive from direct activation and protection of sGC function. A sGC‐directed action may explain the more pronounced cardiovascular benefit of gemfibrozil observed over other fibrates and some of the described side effects of gemfibrozil.

01 Apr 2015·Current Opinion in PharmacologyQ2 · MEDICINE

Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence

Q2 · MEDICINE

Review

Author: Jens Schlossmann ; Berthold Hocher ; Johannes Peter Stasch

Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD). Therefore, new classes of drugs - sGC stimulators and activators - are being investigated in preclinical models under conditions where nitric oxide is deficient. In preclinical models with different etiologies of CKD, the sGC stimulators BAY 41-2272, BAY 41-8543, BAY 60-4552, riociguat and vericiguat and the sGC activators cinaciguat, ataciguat, BI 703704 and GSK2181236A have shown consistently renoprotective effects. Clinical trials are required to confirm these findings in humans, and to ascertain whether these agents could provide a future alternative to guideline-recommended treatments.

100 Deals associated with Ataciguat

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12805

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Intermittent Claudication	Phase 2	CA	Sanofi SA	01 Feb 2007
Intermittent Claudication	Phase 2	FR	Sanofi SA	01 Feb 2007
Intermittent Claudication	Phase 2	PL	Sanofi SA	01 Feb 2007
Intermittent Claudication	Phase 2	AT	Sanofi SA	01 Feb 2007
Intermittent Claudication	Phase 2	RU	Sanofi SA	01 Feb 2007
Intermittent Claudication	Phase 2	ZA	Sanofi SA	01 Feb 2007
Intermittent Claudication	Phase 2	US	Sanofi SA	01 Feb 2007
Peripheral Arterial Disease	Phase 2	AT	Sanofi SA	01 Feb 2007
Peripheral Arterial Disease	Phase 2	PL	Sanofi SA	01 Feb 2007
Peripheral Arterial Disease	Phase 2	FR	Sanofi SA	01 Feb 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02481258 (CAVS, CTgov)	Phase 2	Aortic Valve, Calcification Of	35	Ataciguat (HMR1766) (Ataciguat (HMR1766))	iaixkouluz(sxglygbjsj) = yjrbxtywdy qsrtlfyfue (ssqxivhexe, hcdcutaetl - pclavxfnzd) View more	-	18 Jan 2020
				Placebo Comparator: Matching Placebo (Matching Placebo)	iaixkouluz(sxglygbjsj) = hbrtdkwjbw qsrtlfyfue (ssqxivhexe, cwveyuexvs - nkfckxbnua) View more