Delving into the Latest Updates on NGP-555 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

γ-secretase

Mechanism

γ-secretase inhibitors(Gamma-secretase inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Alzheimer Disease

Originator Organization

NeuroGenetic Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

NeuroGenetic Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC23H23FN4S

InChIKeyWDEKUGNKKOGFOA-UHFFFAOYSA-N

CAS Registry1304630-27-0

AbstractIntroductionCurrently, 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.MethodsUsing 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.ResultsOur 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.DiscussionIn 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.

01 Jan 2017·Alzheimer's & Dementia: Translational Research & Clinical Interventions

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

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

AbstractIntroductionAlzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years.MethodsUsing amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques, we investigate the properties of NGP 555, a clinical‐stage γ‐secretase modulator.ResultsNGP 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.DiscussionAbundant 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.

01 Oct 2010·IDrugs : the investigational drugs journal

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

Author: 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 Deals associated with NGP-555

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