NGP-555(NGP-555) - 药物靶点：γ-secretase_专利_临床

概要

基本信息

药物类型

小分子化药

别名

NGP 555、NGX-555

靶点

γ-secretase

作用机制

γ-secretase抑制剂(γ-分泌酶复合体抑制剂)

治疗领域

神经系统疾病

在研适应症-

非在研适应症

阿尔茨海默症

原研机构

NeuroGenetic Pharmaceuticals, Inc.

在研机构-

非在研机构

NeuroGenetic Pharmaceuticals, Inc.

最高研发阶段无进展临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C23H23FN4S

InChIKeyWDEKUGNKKOGFOA-UHFFFAOYSA-N

CAS号1304630-27-0

关联

2

项与 NGP-555 相关的临床试验

NCT02537938

/ Completed临床1期

A Randomized, Placebo-Controlled, Double-blind, Parallel-Group, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally-administered NGP 555 in Healthy Subjects

This study involves the use of an investigational drug called NGP 555. In each group of healthy subjects, 2 people will receive placebo and 6 people will receive NGP 555.

开始日期2016-01-01

申办/合作机构

NeuroGenetic Pharmaceuticals, Inc.

[+1]

NCT02534480

/ Completed临床1期

A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally-administered NGP 555 in Healthy Young Volunteers

NGP 555 is a small molecule preventative therapy aimed at reducing Alzheimer's disease amyloid buildup by targeting Abeta 42 production.

开始日期2015-03-01

申办/合作机构

NeuroGenetic Pharmaceuticals, Inc.

100 项与 NGP-555 相关的临床结果

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100 项与 NGP-555 相关的转化医学

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100 项与 NGP-555 相关的专利（医药）

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3

项与 NGP-555 相关的文献（医药）

2019-01-01·Alzheimer's & dementia (New York, N. Y.)

NGP 555, a γ‐secretase modulator, shows a beneficial shift in the ratio of amyloid biomarkers in human cerebrospinal fluid at safe doses

Article

作者: Durakoglugil, Murat S. ; Comer, William T. ; Kounnas, Maria Z. ; Herz, Joachim

Abstract:

Introduction:

Currently, there is no cure for Alzheimer's disease (AD), and it is widely accepted that AD is a complex disease with multiple approaches necessary to prevent and treat the disease.

Methods:

Using amyloid biomarkers in human cerebrospinal fluid, pharmacokinetic, safety, and metabolism studies, we investigate the properties of NGP 555, γ‐secretase modulator, for the first time in human clinical trials.

Results:

Our preclinical and clinical studies combined show beneficial effects with NGP 555 on synaptic response and amyloid cerebrospinal fluid biomarkers while avoiding negative side effects. Importantly, pharmacokinetic and pharmacodynamic parameters combined with safety outcomes indicate that NGP 555 penetrates the blood‐brain barrier and increases the ratio of amyloid‐β peptide Aβ37 and Aβ38 compared with that of Aβ42, establishing a proof of target engagement in humans in a 14 day, once‐daily oral dosing trial.

Discussion:

In humans, NGP 555 has demonstrated a beneficial shift in the production of Aβ37 and Aβ38 versus Aβ42 biomarker levels in the cerebrospinal fluid while maintaining an adequate safety profile. The overall clinical goal is to achieve an optimal balance of efficacy for altering amyloid‐β peptide (Aβ) biomarkers while maintaining a safe profile so that NGP 555 can be given early in AD to prevent production of Aβ42 and accumulation of amyloid plaques, in an effort to prevent aggregation of tau and destruction of neurons and synapses resulting in cognitive decline.

2017-01-01·Alzheimer's & dementia (New York, N. Y.)

NGP 555, a γ‐secretase modulator, lowers the amyloid biomarker, Aβ_42, in cerebrospinal fluid while preventing Alzheimer's disease cognitive decline in rodents

Article

作者: Nowakowski, Dan W. ; Comer, William T. ; Herz, Joachim ; Lane‐Donovan, Courtney ; Kounnas, Maria Z.

Abstract:

Introduction:

Alzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years.

Methods:

Using amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques, we investigate the properties of NGP 555, a clinical‐stage γ‐secretase modulator.

Results:

NGP 555 shifts amyloid peptide production to the smaller, nonaggregating forms of amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers, pathology, and cognition. NGP 555 has successfully completed chemistry, pharmacology, toxicity, metabolism, and safety studies.

Discussion:

Abundant data support Aβ42 as a target for prophylactic or early‐stage intervention therapies in AD. The γ‐secretase modulator, NGP 555 is being actively developed in human clinical trials for the prevention of Alzheimer's disease with the overall aim to achieve an appropriate balance of potency/efficacy on reducing the toxic forms of amyloid versus safety.

2010-10-01·IDrugs : the investigational drugs journal

American Chemical Society - 240th national meeting - chemistry for preventing and combating disease: part 1.

作者: Burt, Jessica

The 240th National Meeting of the American Chemical Society, held in Boston, included topics covering new therapeutic research. This conference report highlights selected presentations on negative allosteric modulators of metabotropic glutamate receptor 5 (mGluR5) for the treatment of Parkinson's disease, BACE1 inhibitors and γ-secretase inhibitors for the prevention or treatment of Alzheimer's disease, opioid modulators for the treatment of reward disorders, SGLT2 inhibitors for the treatment of diabetes, backup compounds to the DPP-4 inhibitor sitagliptin (Januvia) for type 2 diabetes, and MCH R1 inhibitors for the treatment of obesity. Investigational drugs discussed include SCH-1359113 and SCH-1682496 (both Merck & Co), NGP-555 (NeuroGenetic Pharmaceuticals), ALKS-33 (Alkermes), dapagliflozin (Bristol-Myers Squibb/AstraZeneca) and GSK-882380 (GlaxoSmithKline).

100 项与 NGP-555 相关的药物交易

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