Phenserine tartrate(Phenserine tartrate) - 药物靶点：AChE x amylin_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(-)-eseroline phenylcarbamate、(-)-phenserine、Phenserine

+ [1]

靶点

AChE x amylin

作用机制

AChE抑制剂(乙酰胆碱酯酶抑制剂)、amylin抑制剂(胰岛淀粉样多肽抑制剂)

治疗领域

神经系统疾病其他疾病

在研适应症-

非在研适应症

阿尔茨海默症中毒

原研机构

Annovis Bio, Inc.

在研机构-

非在研机构

Daewoong Pharmaceutical Co., Ltd.

Annovis Bio, Inc.Cenomed BioSciences LLC

最高研发阶段终止临床阶段不明

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C20H23N3O2

InChIKeyPBHFNBQPZCRWQP-QUCCMNQESA-N

CAS号101246-66-6

查看全部结构式(2)

关联

5

项与 Phenserine tartrate 相关的临床试验

EUCTR2005-000063-25-GB / Not yet recruiting临床3期

A 26 week double-blind extension to a 26 week randomised, double-blind placebo-controlled study that evaluated the safety and efficacy of two different doses of phenserine-tartrate in patients with probable mild to moderate Alzheimer's disease.

开始日期2005-06-10

申办/合作机构

Axonyx, Inc.

EUCTR2004-000933-12-ES / Unknown statusN/A

A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of two different doses of phenserine-tartrate in patients with probable mild to moderate Alzheimer’s disease

开始日期2005-02-22

申办/合作机构

Axonyx, Inc.

EUCTR2004-001187-52-LV / Not yet recruitingN/A

A Randomised, Double-Blind, Placebo-Controlled Trialto Evaluate the Safety and Efficacy of Two DifferentDosages of Phenserine-tartrate in Patients with Mild toModerate Probable Alzheimer’s Disease -Phenserine/APP and Aß

开始日期2004-11-12

申办/合作机构

Axonyx, Inc.

100 项与 Phenserine tartrate 相关的临床结果

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100 项与 Phenserine tartrate 相关的转化医学

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100 项与 Phenserine tartrate 相关的专利（医药）

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83

项与 Phenserine tartrate 相关的文献（医药）

2022-02-11·ACS Pharmacology & Translational Science

In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes

Article

作者: Furqan, Tiyyaba ; Hasan Mahmood, Muhammad Sibte ; Greig, Nigel H. ; Batool, Sidra ; Kamal, Mohammad A. ; Tweedie, David

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Ongoing research to develop AD treatments has characterized multiple drug targets including the cholinergic system, amyloid-β peptide, phosphorylated tau, and neuroinflammation. These systems have the potential to interact to either drive or slow AD progression. Promising agents that simultaneously impact many of these drug targets are the AD experimental drug Posiphen and its enantiomer phenserine that, currently, are separately being evaluated in clinical trials. To define the cholinergic component of these agents, the anticholinesterase activities of a ligand dataset comprising Posiphen and primary metabolites ((+)-N1-norPosiphen, (+)-N8-norPosiphen, and (+)-N1,N8-bisnorPosiphen) were characterized and compared to those of the enantiomer phenserine. The "target" dataset involved the human cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Binding interactions between the ligands and targets were analyzed using Autodock 4.2. The computationally determined inhibitory action of these ligands was then compared to ex vivo laboratory-measured values versus human AChE and BChE. While Posiphen lacked AChE inhibitory action, its major and minor metabolites (+)-N1-norPosiphen and (+)-N1,N8-bisnorPosiphen, respectively, possessed modest AChE inhibitory activity, and Posiphen and all metabolites lacked BChE action. Phenserine, as a positive control, demonstrated AChE-selective inhibitory action. In light of AChE inhibitory action deriving from a major and minor Posiphen metabolite, current Posiphen clinical trials in AD and related disorders should additionally evaluate AChE inhibition; particularly if Posiphen should be combined with a known anticholinesterase, since this drug class is clinically approved and the standard of care for AD subjects, and excessive AChE inhibition may impact drug tolerability.

2021-08-20·Organic Letters1区 · 化学

Mutasynthesis of Physostigmines in Myxococcus xanthus

1区 · 化学

Article

作者: Kaiser, Marcel ; Greven, Nico-Joel ; Nett, Markus ; Hiller, Wolf ; Pietruszka, Jörg ; Winand, Lea ; Schneider, Pascal ; Kruth, Sebastian

The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by applying a simple feeding strategy include the promising drug candidate phenserine, which was previously accessible only by total synthesis.

2020-06-01·CNS Neuroscience & Therapeutics2区 · 医学

(−)‐Phenserine tartrate (PhenT) as a treatment for traumatic brain injury

2区 · 医学

ReviewOA

作者: Hsueh, Shih‐Chang ; Glotfelty, Elliot J. ; Chiang, Yung‐Hsiao ; Hoffer, Barry J. ; Greig, Nigel H. ; Tweedie, David ; Becker, Robert E. ; Lecca, Daniela ; Nogueras‐Ortiz, Carlos ; Kapogiannis, Dimitrios

AbstractAimTraumatic brain injury (TBI) is one of the most common causes of morbidity and mortality of both young adults and the elderly, and is a key contributing factor in about 30% of all injury‐associated deaths occurring within the United States of America. Albeit substantial impact has been made to improve our comprehension of the mechanisms that underpin the primary and secondary injury stages initiated by a TBI incident, this knowledge has yet to successfully translate into the development of an effective TBI pharmacological treatment. Developing consent suggests that a TBI can concomitantly trigger multiple TBI‐linked cascades that then progress in parallel and, if correct, the multifactorial nature of TBI would make the discovery of a single effective mechanism‐targeted drug unlikely.DiscussionWe review recent data indicating that the small molecular weight drug (−)‐phenserine tartrate (PhenT), originally developed for Alzheimer's disease (AD), effectively inhibits a broad range of mechanisms pertinent to mild (m) and moderate (mod)TBI, which in combination underpin the ensuing cognitive and motor impairments. In cellular and animal models at clinically translatable doses, PhenT mitigated mTBI‐ and modTBI‐induced programmed neuronal cell death (PNCD), oxidative stress, glutamate excitotoxicity, neuroinflammation, and effectively reversed injury‐induced gene pathways leading to chronic neurodegeneration. In addition to proving efficacious in well‐characterized animal TBI models, significantly mitigating cognitive and motor impairments, the drug also has demonstrated neuroprotective actions against ischemic stroke and the organophosphorus nerve agent and chemical weapon, soman.ConclusionIn the light of its tolerability in AD clinical trials, PhenT is an agent that can be fast‐tracked for evaluation in not only civilian TBI, but also as a potentially protective agent in battlefield conditions where TBI and chemical weapon exposure are increasingly jointly occurring.

100 项与 Phenserine tartrate 相关的药物交易

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