Delving into the Latest Updates on Derenofylline with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

A1R

Action

antagonists

Mechanism

A1R antagonists(Adenosine A1 receptor antagonists)

Therapeutic Areas

NeoplasmsCardiovascular DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Acute decompensated heart failureHeart FailureRenal Cell Carcinoma

Originator Organization

Abbott Laboratories

Active Organization-

Inactive Organization

Solvay Pharmaceuticals, Inc.

Solvay SA

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC18H20N4O

InChIKeyRBZNJGHIKXAKQE-HDJSIYSDSA-N

CAS Registry251945-92-3

This is a randomized, double-blind, placebo-controlled, multi-center, sequential cohort study in subjects with congestive heart failure (CHF) and impaired renal function who are on stable furosemide treatment (³ 40 mg daily). A total of 50 subjects will be randomized to each increasing dose level of SLV320 or placebo in a sequential fashion.

Start Date01 Oct 2007

Sponsor / Collaborator

Solvay Pharmaceuticals, Inc.

[+1]

NCT00160134

/ CompletedPhase 2

A Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Parallel Group, Single Dose Study to Evaluate Cardiac Hemodynamics and Safety During Right Heart Catheterization of Three IV Doses of SLV320 in Subjects With Congestive Heart Failure Requiring Diuretic Treatment

The study is a randomized, placebo controlled, multi-center, single dose study to evaluate cardiac hemodynamics and safety of iv SLV320 in 110 subjects with congestive heart failure requiring diuretic treatment. Each subject will receive one dose of SLV320 or placebo or furosemide. The study consists of three visits (or study days when in-subjects are included). Ambulatory subjects will be in hospital for two nights and one day.

Start Date01 Jan 2005

Sponsor / Collaborator

Solvay Pharmaceuticals, Inc.

100 Clinical Results associated with Derenofylline

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100 Translational Medicine associated with Derenofylline

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100 Patents (Medical) associated with Derenofylline

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25

Literatures (Medical) associated with Derenofylline

01 Aug 2024·Pharmacology Research & Perspectives

A novel and selective fluorescent ligand for the study of adenosine A_2B receptors

Article

Author: Kellam, Barrie ; Franks, Hester ; Kilpatrick, Laura E. ; Kindon, Nicholas D. ; Goulding, Joelle ; Comeo, Eleonora ; Hill, Stephen J. ; Mistry, Sarah J. ; Patera, Foteini

AbstractFluorescent ligands have proved to be powerful tools in the study of G protein‐coupled receptors in living cells. Here we have characterized a new fluorescent ligand PSB603‐BY630 that has high selectivity for the human adenosine A2B receptor (A2BR). The A2BR appears to play an important role in regulating immune responses in the tumor microenvironment. Here we have used PSB603‐BY630 to monitor specific binding to A2BRs in M1‐ and M2‐like macrophages derived from CD14+ human monocytes. PSB603‐BY630 bound with high affinity (18.3 nM) to nanoluciferase‐tagged A2BRs stably expressed in HEK293G cells. The ligand exhibited very high selectivity for the A2BR with negligible specific‐binding detected at NLuc‐A2AR, NLuc‐A1R, or NLuc‐A3R receptors at concentrations up to 500 nM. Competition binding studies showed the expected pharmacology at A2BR with the A2BR‐selective ligands PSB603 and MRS‐1706 demonstrating potent inhibition of the specific binding of 50 nM PSB603‐BY630 to A2BR. Functional studies in HEK293G cells using Glosensor to monitor Gs‐coupled cyclic AMP responses indicated that PSB603‐BY630 acted as a negative allosteric regular of the agonist responses to BAY 60–6583. Furthermore, flow cytometry analysis confirmed that PSB603‐BY630 could be used to selectively label endogenous A2BRs expressed on human macrophages. This ligand should be an important addition to the library of fluorescent ligands which are selective for the different adenosine receptor subtypes, and will enable study of the role of A2BRs on immune cells in the tumor microenvironment.

01 Aug 2021·Pharmacology Research & PerspectivesQ4 · MEDICINE

Effects of sevoflurane and adenosine receptor antagonist on the sugammadex‐induced recovery from rocuronium‐induced neuromuscular blockade in rodent phrenic nerve–hemidiaphragm tissue specimens

Q4 · MEDICINE

ArticleOA

Author: Kim, Yong Beom ; In, Junyong ; Park, Chungon ; Choi, Hey‐Ran ; Yang, Hong‐Seuk ; Choi, Jae‐Moon

AbstractSevoflurane affects on the A1 receptor in the central nervous system and potentiates the action of neuromuscular blocking agents. In the present study, we investigated whether sevoflurane (SEVO) has the ability to potentiate the neuromuscular blocking effect of rocuronium and if the specific antagonist of adenosine receptor (SLV320) can reverse this effect. In this study, phrenic nerve–hemidiaphragm tissue specimens were obtained from 40 Sprague–Dawley (SD) rats. The specimens were immersed in an organ bath filled with Krebs buffer and stimulated by a train‐of‐four (TOF) pattern using indirect supramaximal stimulation at 20 s intervals. The specimens were randomly allocated to control, 2‐chloroadenosine (CADO), SEVO, or SLV320 + SEVO groups. In the CADO and SLV320 + SEVO groups, CADO and SLV320 were added to the organ bath from the start to a concentration of 10 μM and 10 nM, respectively. We then proceeded with rocuronium‐induced blockade of >95% depression of the first twitch tension of TOF (T1) and TOF ratio (TOFR). In the SEVO and SLV320 + SEVO groups, SEVO was added to the Krebs buffer solution to concentration of 400–500 μM for 10 min. Sugammadex‐induced T1 and TOFR recovery was monitored for 30 min until >95% of T1 and >0.9 of TOFR were confirmed, and the recovery pattern was compared by plotting these data. T1 recovery in the SEVO and CADO groups was significantly delayed compared with the control and SLV320 + SEVO groups (p < .05). In conclusion, sevoflurane affects on the A1 receptor at the neuromuscular junction and delays sugammadex‐induced recovery from neuromuscular blockade.

24 Jun 2021·Journal of Medicinal ChemistryQ1 · MEDICINE

Development of Covalent, Clickable Probes for Adenosine A₁ and A₃ Receptors

Q1 · MEDICINE

Article

Author: Gregory, Karen J. ; Trinh, Phuc N. H. ; Vernall, Andrea J. ; Chong, Daniel J. W. ; Tyndall, Joel D. A. ; Hill, Stephen J. ; May, Lauren T. ; Leach, Katie

Adenosine receptors are attractive therapeutic targets for multiple conditions, including ischemia-reperfusion injury and neuropathic pain. Adenosine receptor drug discovery efforts would be facilitated by the development of appropriate tools to assist in target validation and direct receptor visualization in different native environments. We report the development of the first bifunctional (chemoreactive and clickable) ligands for the adenosine A₁ receptor (A₁R) and adenosine A₃ receptor (A₃R) based on an orthosteric antagonist xanthine-based scaffold and on an existing structure-activity relationship. Bifunctional ligands were functional antagonists with nanomolar affinity and irreversible binding at the A₁R and A₃R. In-depth pharmacological profiling of these bifunctional ligands showed moderate selectivity over A_2A and A_2B adenosine receptors. Once bound to the receptor, ligands were successfully "clicked" with a cyanine-5 fluorophore containing the complementary "click" partner, enabling receptor detection. These bifunctional ligands are expected to aid in the understanding of A₁R and A₃R localization and trafficking in native cells and living systems.

100 Deals associated with Derenofylline

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute decompensated heart failure	Phase 2	Italy	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	France	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Russia	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Germany	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Ukraine	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Canada	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Denmark	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Romania	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Acute decompensated heart failure	Phase 2	Poland	Solvay Pharmaceuticals, Inc.	01 Feb 2009
Heart Failure	Phase 2	United States	Solvay SA	-