Characterization of FRM-36143 as a new γ-secretase modulator for the potential treatment of familial Alzheimer’s disease

Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery

(2016) Travis T. Wager et al.   ACS Chemical Neuroscience

Generation and deposition of Aβ43 by the virtually inactive presenilin‐1 L435F mutant contradicts the presenilin loss‐of‐function hypothesis of Alzheimer's disease

(2016) Benedikt Kretner et al.   EMBO Molecular Medicine

Gamma Secretase Modulators: New Alzheimer’s Drugs on the Horizon?

(2016) Matthew G. Bursavich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Alzheimer's disease

(2016) Philip Scheltens et al.   LANCET

Qualitative changes in human γ-secretase underlie familial Alzheimer’s disease

(2015) Maria Szaruga et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Lessons from a Failed γ-Secretase Alzheimer Trial

(2014) Bart De Strooper   CELL

Safety profile of semagacestat, a gamma-secretase inhibitor: IDENTITY trial findings

(2014) David B. Henley et al.   CURRENT MEDICAL RESEARCH AND OPINION

Molecular Mechanisms of Alzheimer Disease Protection by the A673T Allele of Amyloid Precursor Protein

(2014) Janice A. Maloney et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects

(2014) Robert Vassar et al.   JOURNAL OF NEUROCHEMISTRY

β-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage

(2014) Erik Portelius et al.   Alzheimers Research & Therapy

A fast growing spectrum of biological functions of γ-secretase in development and disease

(2013) Nathalie Jurisch-Yaksi et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators

(2013) Daniel Oehlrich et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

γ-Secretase Associated with Lipid Rafts

(2013) Nobutaka Matsumura et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel γ-secretase modulator, E2212, in healthy human subjects

(2013) Yanke Yu et al.   JOURNAL OF CLINICAL PHARMACOLOGY

A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease

(2013) Rachelle S. Doody et al.   NEW ENGLAND JOURNAL OF MEDICINE

E2012-Induced Cataract and Its Predictive Biomarkers

(2013) K. Nakano-Ito et al.   TOXICOLOGICAL SCIENCES

γ-Secretase Modulators and Presenilin 1 Mutants Act Differently on Presenilin/γ-Secretase Function to Cleave Aβ42 and Aβ43

(2013) Masayasu Okochi et al.   Cell Reports

Safety and Tolerability of the γ-Secretase Inhibitor Avagacestat in a Phase 2 Study of Mild to Moderate Alzheimer Disease

(2012) Vladimir Coric et al.   ARCHIVES OF NEUROLOGY

The mechanism of γ-Secretase dysfunction in familial Alzheimer disease

(2012) Lucía Chávez-Gutiérrez et al.   EMBO JOURNAL

Differential Effects between  -Secretase Inhibitors and Modulators on Cognitive Function in Amyloid Precursor Protein-Transgenic and Nontransgenic Mice

(2012) Y. Mitani et al.   JOURNAL OF NEUROSCIENCE

Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice

(2012) Kathryn Rogers et al.   Molecular Neurodegeneration

A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline

(2012) Thorlakur Jonsson et al.   NATURE

The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

(2012) Iryna Benilova et al.   NATURE NEUROSCIENCE

BACE1 Inhibition Induces a Specific Cerebrospinal Fluid β-Amyloid Pattern That Identifies Drug Effects in the Central Nervous System

(2012) Niklas Mattsson et al.   PLoS One

Attenuated Aβ42Responses to Low Potency γ-Secretase Modulators Can Be Overcome for Many Pathogenic Presenilin Mutants by Second-generation Compounds

(2011) Benedikt Kretner et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Potent amyloidogenicity and pathogenicity of Aβ43

(2011) Takashi Saito et al.   NATURE NEUROSCIENCE

The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics

(2011) Eric Karran et al.   NATURE REVIEWS DRUG DISCOVERY

Defining Desirable Central Nervous System Drug Space through the Alignment of Molecular Properties, in Vitro ADME, and Safety Attributes

(2010) Travis T. Wager et al.   ACS Chemical Neuroscience

Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties

(2010) Travis T. Wager et al.   ACS Chemical Neuroscience

Distinct cerebrospinal fluid amyloid β peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease

(2010) Erik Portelius et al.   Molecular Neurodegeneration

Alzheimer's Disease

(2010) Henry W. Querfurth et al.   NEW ENGLAND JOURNAL OF MEDICINE

Synaptic activity prompts γ-secretase–mediated cleavage of EphA4 and dendritic spine formation

(2009) Eiji Inoue et al.   JOURNAL OF CELL BIOLOGY

Aβ43 is more frequent than Aβ40 in amyloid plaque cores from Alzheimer disease brains

(2009) Hedvig Welander et al.   JOURNAL OF NEUROCHEMISTRY

 -Secretase: Successive Tripeptide and Tetrapeptide Release from the Transmembrane Domain of  -Carboxyl Terminal Fragment

(2009) M. Takami et al.   JOURNAL OF NEUROSCIENCE

Enzymatic Characteristics of I213T Mutant Presenilin-1/γ-Secretase in Cell Models and Knock-in Mouse Brains

(2008) Masafumi Shimojo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY