Delving into the Latest Updates on AER-271 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [3]

Target

AQP4

Mechanism

AQP4 inhibitors(Aquaporins 4 inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication

Acute Ischemic StrokeBrain Edema

Inactive Indication-

Originator Organization

Simcere Pharmaceutical Group Ltd.

Aeromics, Inc.

Active Organization

Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.

Inactive Organization

Jiangsu Simcere Pharmaceutical Co., Ltd.

Aeromics, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC15H9ClF6NNa2O5P

InChIKeyRVICWTABTCUYJS-UHFFFAOYSA-N

CAS Registry1485066-29-2

View All Structures (2)

主要研究目的评价注射用SIM1910-09在中国健康成人受试者中的耐受性和安全性。次要研究目的评价注射用SIM1910-09在中国健康成人受试者中单次/多次给药后， SIM1910-09及活性代谢物 SCR-6401的药代动力学特征。探索性研究目的评价注射用SIM1910-09在中国健康成人受试者中单次/多次给药后，血液中SIM1910-09及活性代谢物SCR-6401在体外对细胞因子释放的作用。

[Translation]

Main study objectives To evaluate the tolerability and safety of SIM1910-09 for injection in healthy Chinese adult subjects. Secondary study objectives To evaluate the pharmacokinetic characteristics of SIM1910-09 and its active metabolite SCR-6401 after single/multiple administration of SIM1910-09 for injection in healthy Chinese adult subjects. Exploratory study objectives To evaluate the effects of SIM1910-09 and its active metabolite SCR-6401 on cytokine release in vitro in the blood after single/multiple administration of SIM1910-09 for injection in healthy Chinese adult subjects.

Start Date06 Dec 2021

Sponsor / Collaborator

Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.

NCT03804476 / CompletedPhase 1

A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Sequential-Group Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of AER-271 in Healthy Subjects

The objective of this Phase 1 trial is to assess the safety, tolerability and pharmacokinetics of AER-271 in health subjects.

Start Date26 Jun 2018

Sponsor / Collaborator

Aeromics, Inc.

[+1]

100 Clinical Results associated with AER-271

Login to view more data

100 Translational Medicine associated with AER-271

Login to view more data

100 Patents (Medical) associated with AER-271

Login to view more data

6

Literatures (Medical) associated with AER-271

01 May 2024·Glia

Glymphatic fluid transport is suppressed by the aquaporin‐4 inhibitor AER‐271

Article

Author: Newbold, Evan J ; Thompson, Trevor ; Giannetto, Michael J ; Gahn-Martinez, Daniel ; Gomolka, Ryszard S ; Nedergaard, Maiken ; Mori, Yuki ; Chang, Ethan ; Bork, Peter A R ; Gresser, Michael

AbstractThe glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin‐4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space. Yet, prior studies of AQP4 function have relied on genetic models, or correlated altered AQP4 expression with glymphatic flow in disease states. Herein, we sought to pharmacologically manipulate AQP4 function with the inhibitor AER‐271 to assess the contribution of AQP4 to glymphatic fluid transport in mouse brain. Administration of AER‐271 inhibited glymphatic influx as measured by CSF tracer infused into the cisterna magna and inhibited increases in the interstitial fluid volume as measured by diffusion‐weighted MRI. Furthermore, AER‐271 inhibited glymphatic efflux as assessed by an in vivo clearance assay. Importantly, AER‐271 did not affect AQP4 localization to the astrocytic endfeet, nor have any effect in AQP4 deficient mice. Since acute pharmacological inhibition of AQP4 directly decreased glymphatic flow in wild‐type but not in AQP4 deficient mice, we foresee AER‐271 as a new tool for manipulation of the glymphatic system in rodent brain.

01 Apr 2019·Neuroscience

Functionalized Phenylbenzamides Inhibit Aquaporin-4 Reducing Cerebral Edema and Improving Outcome in Two Models of CNS Injury

Article

Author: Farr, Susan M ; LaManna, Joseph C ; Buch, Jasen M ; Xu, Kui ; Adams, Amielia G ; McGuirk, Paul R ; Flask, Christopher A ; Wade, Ramon ; Detzel, Joshua M ; Boron, Walter F ; Pelletier, Marc F ; Hall, Christopher H ; Beahm, Derek L ; Farr, George W

Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema water enters the brain by moving across an intact blood brain barrier and through aquaporin-4 (AQP4) at astrocyte endfeet. Using AQP4-expressing cells, we screened small molecule libraries for inhibitors that reduce AQP4-mediated water permeability. Additional functional assays were used to validate AQP4 inhibition and identified a promising structural series for medicinal chemistry. These efforts improved potency and revealed a compound we designated AER-270, N-[3,5-bis (trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide. AER-270 and a prodrug with enhanced solubility, AER-271 2-{[3,5-Bis(trifluoromethyl) phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, improved neurological outcome and reduced swelling in two models of CNS injury complicated by cerebral edema: water intoxication and ischemic stroke modeled by middle cerebral artery occlusion.

01 Mar 2019·Pediatric ResearchQ3 · MEDICINE

The aquaporin-4 inhibitor AER-271 blocks acute cerebral edema and improves early outcome in a pediatric model of asphyxial cardiac arrest

Q3 · MEDICINE

Article

Author: Clark, Robert S B ; Pelletier, Marc F ; Wallisch, Jessica S ; Jackson, Travis C ; McGuirk, Paul R ; Janesko-Feldman, Keri ; Kochanek, Patrick M ; Kline, Anthony E ; Manole, Mioara D ; Farr, George W ; Alexander, Henry ; Jha, Ruchira M

BACKGROUNDCerebral edema after cardiac arrest (CA) is associated with increased mortality and unfavorable outcome in children and adults. Aquaporin-4 mediates cerebral water movement and its absence in models of ischemia improves outcome. We investigated early and selective pharmacologic inhibition of aquaporin-4 in a clinically relevant asphyxial CA model in immature rats in a threshold CA insult that produces primarily cytotoxic edema in the absence of blood-brain barrier permeability.METHODSPostnatal day 16-18 Sprague-Dawley rats were studied in our established 9-min asphyxial CA model. Rats were randomized to aquaporin-4 inhibitor (AER-271) vs vehicle treatment, initiated at return of spontaneous circulation. Cerebral edema (% brain water) was the primary outcome with secondary assessments of the Neurologic Deficit Score (NDS), hippocampal neuronal death, and neuroinflammation.RESULTSTreatment with AER-271 ameliorated early cerebral edema measured at 3 h after CA vs vehicle treated rats. This treatment also attenuated early NDS. In contrast to rats treated with vehicle after CA, rats treated with AER-271 did not develop significant neuronal death or neuroinflammation as compared to sham.CONCLUSIONEarly post-resuscitation aquaporin-4 inhibition blocks the development of early cerebral edema, reduces early neurologic deficit, and blunts neuronal death and neuroinflammation post-CA.

100 Deals associated with AER-271

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 1	CN	Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.	06 Dec 2021
Brain Edema	Phase 1	CN	Nanjing Simcere Dongyuan Pharmaceutical Co. Ltd.	06 Dec 2021
Stroke	Preclinical	CN	Jiangsu Simcere Pharmaceutical Co., Ltd.	02 Nov 2021
Ischemic stroke	Preclinical	US	Aeromics, Inc.	26 Jun 2018