Delving into the Latest Updates on RV-568 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

SRC inhibitors(Tyrosine-protein kinase SRC inhibitors), p38α inhibitors(P38 α mitogen-activated protein kinase inhibitors), p38γ inhibitors(P38 γ mitogen-activated protein kinase inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesOtorhinolaryngologic Diseases+ [1]

Active Indication-

Inactive Indication

Pulmonary Disease, Chronic ObstructiveRespiratory Syncytial Virus InfectionsRhinitis, Allergic, Seasonal+ [1]

Originator Organization

RespiVert Ltd.

Active Organization-

Inactive Organization

Janssen Research & Development LLC

RespiVert Ltd.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC34H36N6O4

InChIKeyRTDCVLCTBQDLBW-UHFFFAOYSA-N

CAS Registry1220626-82-3

RV568 is being developed as a possible treatment of smoking related lung disease (also known as Chronic Obstructive Pulmonary Disease - COPD).
The main purpose of this study is to examine the safety and tolerability of a new inhaled formulation of RV568 in healthy volunteers. The study will be run in two parts; Part A and Part B. Part A (Cohorts 1, 2 & 3) will investigate 6 different dose levels of RV568 given as a single dose and Part B (Cohorts 4 & 5) will investigate 2 different dose levels of RV568 given once a day for 14 days.

Start Date01 Sep 2012

Sponsor / Collaborator

RespiVert Ltd.

NCT01475292 / CompletedPhase 2

A Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety and Tolerability of Treatment With Repeat Doses of Inhaled RV568 in Patients With COPD

RV568 is being developed as a possible treatment of diseases such as smoking related lung disease (also known as Chronic Obstructive Pulmonary Disease - COPD) and asthma.
The main purpose of this study is to examine the safety of RV568 in COPD patients. Two dose strengths of RV568 and a placebo will be tested in this study, which will be given by inhaling a liquid suspension from a nebuliser once a day for 2 weeks.

Start Date01 Nov 2011

Sponsor / Collaborator

RespiVert Ltd.

100 Clinical Results associated with RV-568

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100 Translational Medicine associated with RV-568

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100 Patents (Medical) associated with RV-568

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3

Literatures (Medical) associated with RV-568

01 Oct 2017·European Respiratory JournalQ1 · MEDICINE

RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-α and -γ selectivity, suppresses COPD inflammation

Q1 · MEDICINE

Article

Author: Singh, Dave ; Russell, Paul ; Charron, Catherine E ; Kizawa, Yasuo ; Lea, Simon ; Ito, Kazuhiro ; Brindley, Charlie

Novel anti-inflammatory approaches targeting chronically activated kinase pathways in chronic obstructive pulmonary disease (COPD) are needed. We evaluated RV568, a p38 mitogen-activated protein kinase-α and -γ and SRC family kinase inhibitor, in cellular andin vivomodels relevant to COPD and examined its safety and efficacy in COPD patients.The anti-inflammatory activities of RV568 were tested in primary cultured monocytes, macrophages and bronchial epithelial cells andin vivoin lipopolysaccharide and cigarette smoke-exposed murine models. RV568 was evaluated in a 14-day trial in COPD patients.RV568 showed potent anti-inflammatory effects in monocytes and macrophages, which were often greater than those of corticosteroids or the p38 inhibitor Birb796. RV568 combined with corticosteroid had anti-inflammatory effects suggestive of a synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model. In COPD patients, inhaled RV568 (50 µg and 100 µg) improved pre-bronchodilator forced expiratory volume in 1 s (69 mL and 48 mL respectively) and significantly reduced sputum malondialdehyde (p<0.05) compared to placebo, although there were no changes in sputum cell counts. Adverse events during RV568 and placebo treatment were similar.RV568 shows potent anti-inflammatory effects on cell and animal models relevant to COPD. RV568 was well-tolerated and demonstrated a modest clinical benefit in a 14-day COPD clinical trial.

04 Mar 2015·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease

Q2 · MEDICINE

Review

Author: Norman, Peter

INTRODUCTIONThe p38 protein kinases, in particular p38α and p38β, regulate the production of multiple inflammatory mediators. Consequentially, considerable effort has been focused on trying to develop p38 inhibitors for the treatment of inflammatory diseases. Some 20 p38 inhibitors have progressed to clinical development, mostly for the treatment of rheumatoid arthritis, but with little success. Increasingly, interest has turned to their use in other indications and notably chronic obstructive pulmonary disease (COPD).AREAS COVEREDIn this review, the author discusses the eight p38 inhibitors that have been clinically evaluated. Acumapimod is the only one of four orally delivered inhibitors that remains in active development while Phase II results of PH-797804 and losmapimod are compared. The activity of two inhibitors designed for inhaled delivery, RV-568 and PF-03715455, is compared but little is known about AZD-7624 or the discontinued GSK-610677.EXPERT OPINIONResults from animal models provide a clear rationale for developing p38 inhibitors for COPD, and appear to be (partially) validated by the efficacy seen with PH-797804 and losmapimod. Inhaled delivery provides the opportunity to enhance p38 inhibition in the lung while reducing unwanted systemic effects of p38 inhibition. Validation of this hypothesis should come from the results of the recently completed Phase II study with RV-568.

01 Dec 2014·Expert Opinion on Therapeutic PatentsQ2 · MEDICINE

Respivert’s multikinase inhibitors, an evaluation of WO2014033446 to WO2014033449

Q2 · MEDICINE

Article

Author: Norman, Peter

These four patent applications all claim that N-aryl-N'-pyrazol-5-yl urea derivatives , related to RV-568, which are inhibitors of p38, Syk and Src kinases. All four applications claim their use in the treatment of inflammatory diseases, notably asthma and chronic obstructive pulmonary disease. The four applications are primarily differentiated by the claimed substitution of the pyrazole ring. This is accompanied by differential kinase specificity profiles. Many of the exemplified compounds show reduced potency as p38 inhibitors but high potency as inhibitors of Syk and/or Src kinases.

100 Deals associated with RV-568

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Respiratory Syncytial Virus Infections	Phase 2	GB	RespiVert Ltd.	01 Oct 2010
Rhinitis, Allergic, Seasonal	Phase 2	AT	RespiVert Ltd.	01 Oct 2010
Seasonal rhinitis	Preclinical	AT	RespiVert Ltd.	01 Oct 2010
Pulmonary Disease, Chronic Obstructive	Discovery	GB	RespiVert Ltd.	01 Nov 2011