Delving into the Latest Updates on Stresscopin with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

JNJ-39588146, RT 400, RT-400

Target

CRHR2

Action

stimulants

Mechanism

CRHR2 stimulants(Corticotropin-releasing factor receptor 2 stimulants)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Acute decompensated heart failure

Inactive Indication-

Originator Organization

Johnson & Johnson

Active Organization

CLAYTON BIOTECHNOLOGIES, INC.

Inactive Organization

Renova Therapeutics, Inc.Johnson & Johnson Pharmaceutical Research & Development LLC

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9196

Source: *****

The purpose of this study is to investigate the safety, tolerability, pharmacodynamics (how the study medication affects the body) and pharmacokinetics (how the drug is absorbed in the body, how it is distributed within the body and removed from the body over time) of an intravenous administration of JNJ-39588146 or placebo over a 3-hour period in patients with heart failure. The highest tolerated dose received during the first 3 hours of the study will be administered to some patients for an additional 18 hours. There will be up to 3 doses given throughout the administration period over a total of up to 21 hours.

Start Date01 Jun 2010

Sponsor / Collaborator

Johnson & Johnson Pharmaceutical Research & Development LLC

100 Clinical Results associated with Stresscopin

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100 Translational Medicine associated with Stresscopin

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100 Patents (Medical) associated with Stresscopin

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3

Literatures (Medical) associated with Stresscopin

01 Jun 2013·European journal of heart failureQ1 · MEDICINE

Haemodynamic Effects, Safety, and Pharmacokinetics of Human Stresscopin in Heart Failure with Reduced Ejection Fraction

Q1 · MEDICINE

Article

Author: Deckelbaum, Lawrence I. ; Metra, Marco ; Olson, Allan ; Greene, Stephen J. ; Radziszewski, Waldemar ; Grzybowski, Jacek ; Macarie, Cezar ; Gheorghiade, Mihai ; Li, Lilian Y. ; Bueno, Orlando F. ; Ponikowski, Piotr ; Korewicki, Jerzy ; Ghosh, Atalanta ; Bubenek-Turconi, Serban-Ion ; Patel, Ayan R. ; Maggioni, Aldo P. ; Konstam, Marvin A. ; Koester, Andreas

Abstract:

Aims:

Human stresscopin is a corticotropin-releasing factor (CRF) type 2 receptor (CRFR2) selective agonist and a member of the CRF peptide family. Stimulation of CRFR2 improves cardiac output and left ventricular ejection fraction (LVEF) in patients with stable heart failure (HF) with reduced LVEF. We examined the safety, pharmacokinetics, and effects on haemodynamics and serum biomarkers of intravenous human stresscopin acetate (JNJ-9588146) in patients with stable HF with LVEF ≤35% and cardiac index (CI) ≤2.5 L/min/m2.

Methods and results:

Sixty-two patients with HF and LVEF ≤35% were instrumented with a pulmonary artery catheter and randomly assigned (ratio 3:1) to receive an intravenous infusion of JNJ-9588146 or placebo. The main study was an ascending dose study of three doses (5, 15, and 30 ng/kg/min) of study drug or placebo administered in sequential 1 h intervals (3 h total). Statistically significant increases in CI and reduction in systemic vascular resistance (SVR) were observed with both the 15 ng/kg/min (2 h time point) and 30 ng/kg/min (3 h time point) doses of JNJ-9588146 without significant changes in heart rate (HR) or systolic blood pressure (SBP). No statistically significant reductions in pulmonary capillary wedge pressure (PCWP) were seen with any dose tested in the primary analysis, although a trend towards reduction was seen.

Conclusion:

In HF patients with reduced LVEF and CI, ascending doses of JNJ-9588146 were associated with progressive increases in CI and reductions in SVR without significant effects on PCWP, HR, or SBP.Trial registration:NCT01120210

01 Jun 2006·American journal of physiology. Gastrointestinal and liver physiologyQ3 · MEDICINE

CRF-induced calcium signaling in guinea pig small intestine myenteric neurons involves CRF-1 receptors and activation of voltage-sensitive calcium channels

Q3 · MEDICINE

Article

Author: R. Bisschops ; P. Vanden Berghe ; G. Sarnelli ; J. Tack ; J. Janssens

Corticotropin-releasing factor (CRF) is a 41-amino acid peptide with distinct effects on gastrointestinal motility involving both CRF-1 and CRF-2 receptor-mediated mechanisms that are generally claimed to be centrally mediated. Evidence for a direct peripheral effect is rather limited. Electrophysiological studies showed a cAMP-dependent prolonged depolarization of guinea pig myenteric neurons on application of CRF. The current study aimed to test the direct effect of CRF on myenteric neurons and to identify the receptor subtype and the possible mechanisms involved. Longitudinal muscle myenteric plexus preparations and myenteric neuron cultures of guinea pig small intestine were incubated with the calcium indicator Fluo-4. Confocal Ca2+ imaging was used to visualize activation of neurons on application of CRF. All in situ experiments were performed in the presence of nicardipine 10−6 M to reduce tissue movement. Images were analyzed using Scion image and a specifically developed macro to correct for residual minimal movements. A 75 mM K+-Krebs solution identified 1,076 neurons in 46 myenteric ganglia (16 animals). Administration of CRF 10−6 M and CRF 10−7 M during 30 s induced a Ca2+ response in 22.4% of the myenteric neurons ( n = 303). Responses were completely abolished in the presence of the nonselective CRF antagonist astressin ( n = 55). The selective CRF-1 receptor antagonist CP 154,526 ( n = 187) reduced the response significantly to 2.1%. Stresscopin, a CRF-2 receptor agonist, could not activate neurons at 10−7 M, and its effect at 10−6 M (15.3%, n = 59) was completely blocked by CP 154,526. TTX 10−6 M ( n = 70) could not block the CRF-induced Ca2+ transients but reduced the amplitude of the signals significantly. Removal of extracellular Ca2+ blocked all responses to CRF ( n = 47). L-type channels did not contribute to the CRF-induced Ca2+ transients. Blocking N- or P/Q-type Ca2+ channels did not reduce the responses significantly. Combined L- and R-type Ca2+ channel blocking (SNX-482 10−8 M, n = 64) abolished nearly all responses in situ. Combined L-, N-, and P/Q-type channel blocking also significantly reduced the response to 8.6%. Immunohistochemical staining for CRF-1 receptors clearly labeled individual cell bodies in the ganglia, whereas the CRF-2 receptor staining was barely above background. CRF induces Ca2+ transients in myenteric neurons via a CRF-1 receptor-dependent mechanism. These Ca2+ transients highly depend on somatic calcium influx through voltage-operated Ca2+ channels, in particular R-type channels. Action potential firing through voltage-sensitive sodium channels increases the amplitude of the Ca2+ signals. Besides centrally mediated effects, CRF is likely to modulate gastrointestinal motility on the myenteric neuronal level.

01 Mar 2003·General physiology and biophysics

Impaired passive avoidance acquisition in Wistar rats after restraint/cold stress and/or stresscopin administration.

Article

Author: Kaminský, O ; Klenerová, V ; Sída, P ; Hlinák, Z ; Hynie, S ; Krejcí, I

Stresscopin (SCP) and related peptides are new members of the corticotropin-releasing factor (CRF) peptide family that are selective ligands for CRF type 2 receptor; these ligands are essential for maintaining homeostasis after stress. SCP (i.p. injections) was tested on the passive avoidance learning task in stressed Wistar rats; it impaired the formation of memory trace. The retention performance deficit induced by SCP was comparable with the deficit induced by the stressor of restraint/cold. More profound impairment of avoidance response occurred following combined application of SCP and stressor. More specific actions of SCP can be expected from its studies with targeted intracerebral applications.

1

News (Medical) associated with Stresscopin

06 Feb 2017

·renovatherapeutics.com

Renova Therapeutics enters into agreement to receive stresscopin investigational new drug file from Janssen

San Diego, CA – Renova™ Therapeutics, Inc., a biotechnology company developing gene therapy treatments for congestive heart failure and type 2 diabetes, announced today that it has entered into an agreement with Janssen Pharmaceuticals, Inc., whereby the investigational new drug (IND) file for stresscopin – a hormone involved in responses to physiological stress – will be transferred from Janssen, where it was previously under development. Renova Therapeutics plans to advance development of the stresscopin program as RT-400, a peptide infusion treatment for episodes of Acute Decompensated Heart Failure (ADHF). In the United States, ADHF accounts for approximately half of all heart failure-related causes of hospitalization.1 From 2005 to 2010, the average estimated number of ADHF hospitalizations in the U.S. was 1.76 million.2 Annual mortality following an ADHF hospitalization is about 30%.3 “Obtaining this stresscopin program IND helps propel forward the development of our peptide infusion product candidate, RT-400,” said Jack W. Reich, Ph.D., CEO and Co-founder of Renova Therapeutics. “With this data, we hope to see promising results as we initiate pivotal trials.” In addition, Renova Therapeutics holds an exclusive license to the stresscopin peptide from the nonprofit Research Development Foundation. About Acute Decompensated Heart Failure Acute Decompensated Heart Failure (ADHF) is a severe episode of acute respiratory distress in which a heart failure patient experiences a sudden or gradual onset of the signs of heart failure that requires either initiation or escalation of treatment to relieve symptoms and prevent death. ADHF is caused by severe fluid congestion of the body’s organs, especially the lungs, due to the failing heart providing inadequate circulation. Symptoms of ADHF can include difficulty breathing, waking up from sleep gasping for air, fatigue, swelling of the legs or feet, as well as chest pain and pressure. Most episodes require immediate emergency room visits or hospitalizations for treatment. Current treatment options for ADHF primarily involve reducing the organ fluid levels with diuretics, delivered intravenously, and stabilizing heart function with vasodilators such as nitroglycerin. Additional treatments can include providing breathing support using a face mask or breathing tube, as well as an ultrafiltration process to remove fluids in people with ADHF associated with kidney failure. References: 1 Chang PP, Chambless LE, Shahar E, et al. Incidence and Survival of Hospitalized Acute Decompensated Heart Failure in Four US Communities (from the Atherosclerosis Risk in Communities Study). The American journal of cardiology. 2014;113(3):504-510. doi:10.1016/j.amjcard.2013.10.032. 2 Agarwal SK, Wruck L, Quibrera M, et al. Temporal Trends in Hospitalization for Acute Decompensated Heart Failure in the United States, 1998–201. Am. J. Epidemiol. 2016; 183(5):462-470. 3 Dhingra A, Garg A, Kaur S, et al. Epidemiology of heart failure with preserved ejection fraction. Curr Heart Fail Rep. 2014; 11(4):354–365.

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100 Deals associated with Stresscopin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Phase 2	Belgium	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Heart Failure	Phase 2	Germany	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Heart Failure	Phase 2	Poland	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Heart Failure	Phase 2	Romania	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Jun 2010
Acute decompensated heart failure	Preclinical	United States	CLAYTON BIOTECHNOLOGIES, INC.	01 Sep 2025

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Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01120210 (CTgov)	Phase 2	Heart Failure	62	placebo+JNJ-39588146 (Placebo)	luoemaqvev(hstcmzbzez) = bbcsxanfts edvvkqdwfp (jredtnqdpq, 0.19) View more	-	25 Jun 2013
				JNJ-39588146 (JNJ-39588146)	luoemaqvev(hstcmzbzez) = tojvozgang edvvkqdwfp (jredtnqdpq, 0.14) View more

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