Title: A phase 3 trial of semagacestat for treatment of Alzheimer's disease.
Journal: The New England journal of medicine20130725
Title: Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): metabolically stable γ-secretase Inhibitors that selectively inhibit the production of amyloid-β over Notch.
Journal: Journal of medicinal chemistry20130711
Title: The effects on metabolic clearance when administering a potent CYP3A autoinducer with the prototypic CYP3A inhibitor, ketoconazole.
Journal: Drug metabolism and disposition: the biological fate of chemicals20121001
Title: Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants.
Journal: Journal of clinical pharmacology20120601
Title: The mechanism of γ-Secretase dysfunction in familial Alzheimer disease.
Journal: The EMBO journal20120516
Title: miR-9 controls the timing of neurogenesis through the direct inhibition of antagonistic factors.
Journal: Developmental cell20120515
Title: A brain aggregate model gives new insights into the pathobiology and treatment of prion diseases.
Journal: Journal of neuropathology and experimental neurology20120501
Title: First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms.
Journal: The Journal of biological chemistry20120406
Title: Γ-secretase modulators do not induce Aβ-rebound and accumulation of β-C-terminal fragment.
Journal: Journal of neurochemistry20120401
Title: QT effect of semagacestat at therapeutic and supratherapeutic doses.
Journal: International journal of clinical pharmacology and therapeutics20120401
Title: Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice.
Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience20120208
Title: A canine model to evaluate efficacy and safety of γ-secretase inhibitors and modulators.
Journal: Journal of Alzheimer's disease : JAD20120101
Title: Evaluation of the performance of novel Aβ isoforms as theragnostic markers in Alzheimer's disease: from the cell to the patient.
Journal: Neuro-degenerative diseases20120101
Title: Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease.
Journal: Current Alzheimer research20120101
Title: Translatability scoring in drug development: eight case studies.
Journal: Journal of translational medicine20120101
Title: Advances in the identification of γ-secretase inhibitors for the treatment of Alzheimer's disease.
Journal: Expert opinion on drug discovery20120101
Title: Modulation of γ-secretase activity by multiple enzyme-substrate interactions: implications in pathogenesis of Alzheimer's disease.
Journal: PloS one20120101
Title: Silencing of amyloid precursor protein expression using a new engineered delta ribozyme.
Journal: International journal of Alzheimer's disease20120101
Title: Alzheimer's disease and the amyloid cascade hypothesis: a critical review.
Journal: International journal of Alzheimer's disease20120101
Title: Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action.
Journal: International journal of Alzheimer's disease20120101
Title: Alzheimer's disease: a clinical practice-oriented review.
Journal: Frontiers in neurology20120101
Title: Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified γ-secretase complexes.
Journal: PloS one20120101
Title: Amyloid-β(1-15/16) as a marker for γ-secretase inhibition in Alzheimer's disease.
Journal: Journal of Alzheimer's disease : JAD20120101
Title: Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia.
Journal: Molecular neurodegeneration20120101
Title: Predicting cerebral amyloid angiopathy-related intracerebral hemorrhages and other cerebrovascular disorders in Alzheimer's disease.
Journal: Frontiers in neurology20120101
Title: γ-Secretase modulator in Alzheimer's disease: shifting the end.
Journal: Journal of Alzheimer's disease : JAD20120101
Title: pPKCα-mediated effect on in vitro Aβ production in response to gamma secretase inhibitor LY411575 in rat CTXTNA2 astrocytes.
Journal: Journal of biological regulators and homeostatic agents20120101
Title: Quantitative pharmacokinetic/pharmacodynamic analyses suggest that the 129/SVE mouse is a suitable preclinical pharmacology model for identifying small-molecule γ-secretase inhibitors.
Journal: The Journal of pharmacology and experimental therapeutics20111201
Title: [Gamma-secretase inhibitors and modulators].
Journal: Nihon rinsho. Japanese journal of clinical medicine20111201
Title: Metabolism-directed design of oxetane-containing arylsulfonamide derivatives as γ-secretase inhibitors.
Journal: Journal of medicinal chemistry20111124
Title: Current and emerging drug treatment options for Alzheimer's disease: a systematic review.
Journal: Drugs20111022
Title: Pharmacologists and Alzheimer disease therapy: to boldly go where no scientist has gone before.
Journal: Expert opinion on investigational drugs20110901
Title: Drugs: a tangled web of targets.
Journal: Nature20110713
Title: Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer's disease study cohorts from phase 3 trials of semagacestat and solanezumab.
Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association20110701
Title: ACS chemical neuroscience molecule spotlight on ELND006: another γ-secretase inhibitor fails in the clinic.
Journal: ACS chemical neuroscience20110615
Title: Monoclonal antibodies against β-amyloid (Aβ) for the treatment of Alzheimer's disease: the Aβ target at a crossroads.
Journal: Expert opinion on biological therapy20110601
Title: Targets for AD treatment: conflicting messages from γ-secretase inhibitors.
Journal: Journal of neurochemistry20110501
Title: Therapeutic intervention for Alzheimer's disease with γ-secretase inhibitors: still a viable option?
Journal: Expert opinion on investigational drugs20110301
Title: Predicting harms and benefits in translational trials: ethics, evidence, and uncertainty.
Journal: PLoS medicine20110301
Title: What the halted phase III γ-secretase inhibitor trial may (or may not) be telling us.
Journal: Annals of neurology20110201
Title: New pathway links γ-secretase to inflammation and memory while sparing notch.
Journal: Annals of neurology20110101
Title: Suppression of osteosarcoma cell invasion by chemotherapy is mediated by urokinase plasminogen activator activity via up-regulation of EGR1.
Journal: PloS one20110101
Title: Selectivity to amyloid-β precursor protein cleavage provides hope against Alzheimer's.
Journal: Alzheimer's research & therapy20110101
Title: γ-secretase inhibitors and modulators for the treatment of Alzheimer's disease: disappointments and hopes.
Journal: Current topics in medicinal chemistry20110101
Title: Validation of ELISA methods for quantification of total tau and phosporylated-tau181 in human cerebrospinal fluid with measurement in specimens from two Alzheimer's disease studies.
Journal: Journal of Alzheimer's disease : JAD20110101
Title: Glycogen synthase kinase 3 inhibitors in the next horizon for Alzheimer's disease treatment.
Journal: International journal of Alzheimer's disease20110101
Title: Therapeutic promise and challenges of targeting DLL4/NOTCH1.
Journal: Vascular cell20110101
Title: Globalization of Alzheimer's disease clinical trials.
Journal: Alzheimer's research & therapy20110101
Title: Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies.
Journal: Alzheimer's research & therapy20110101
Title: BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells.
Journal: Journal of biomedical science20110101
Title: Interacting with γ-secretase for treating Alzheimer's disease: from inhibition to modulation.
Journal: Current medicinal chemistry20110101
Title: Neuroregenerative mechanisms of allopregnanolone in Alzheimer's disease.
Journal: Frontiers in endocrinology20110101
Title: Genetics. Gamma-secretase and human disease.
Journal: Science (New York, N.Y.)20101119
Title: What can be inferred from the interruption of the semagacestat trial for treatment of Alzheimer's disease?
Journal: Biological psychiatry20101115
Title: REVIEW: γ-Secretase inhibitors for the treatment of Alzheimer's disease: The current state.
Journal: CNS neuroscience & therapeutics20101001
Title: Alzheimer's failure raises questions about disease-modifying strategies.
Journal: Nature reviews. Drug discovery20101001
Title: NerveCenter: Phase III Alzheimer trial halted: Search for therapeutic biomarkers continues.
Journal: Annals of neurology20101001
Title: Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation.
Journal: Anticancer research20101001
Title: ACS chemical neuroscience molecule spotlight on semagacestat (LY450139).
Journal: ACS chemical neuroscience20100818
Title: [Progress in the development of anti-amyloid drugs for treatment of Alzheimer's disease.].
Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica20100701
Title: Disposition and metabolism of semagacestat, a {gamma}-secretase inhibitor, in humans.
Journal: Drug metabolism and disposition: the biological fate of chemicals20100401
Title: Piperidine-derived gamma-secretase modulators.
Journal: Bioorganic & medicinal chemistry letters20100201
Title: In response to 'a gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system'.
Journal: Annals of neurology20100101
Title: A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease.
Journal: Alzheimer's research & therapy20100101
Title: Acute effect on the Aβ isoform pattern in CSF in response to γ-secretase modulator and inhibitor treatment in dogs.
Journal: Journal of Alzheimer's disease : JAD20100101
Title: Brain amyloid β protein and memory disruption in Alzheimer's disease.
Journal: Neuropsychiatric disease and treatment20100101
Title: Use of theragnostic markers to select drugs for phase II/III trials for Alzheimer disease.
Journal: Alzheimer's research & therapy20100101
Title: Could lysine supplementation prevent Alzheimer's dementia? A novel hypothesis.
Journal: Neuropsychiatric disease and treatment20100101
Title: Are γ-secretase inhibitors detrimental for Alzheimer's disease patients?
Journal: Journal of Alzheimer's disease : JAD20100101
Title: Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease.
Journal: Alzheimer's research & therapy20100101
Title: Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
Journal: Journal of medicinal chemistry20091022
Title: Differential effects of gamma-secretase and BACE1 inhibition on brain Abeta levels in vitro and in vivo.
Journal: Journal of neurochemistry20090901
Title: A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system.
Journal: Annals of neurology20090701
Title: Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease.
Journal: Expert opinion on pharmacotherapy20090701
Title: Semagacestat, a gamma-secretase inhibitor for the potential treatment of Alzheimer's disease.
Journal: Current opinion in investigational drugs (London, England : 2000)20090701
Title: gamma-Secretase inhibitor reduces diet-induced atherosclerosis in apolipoprotein E-deficient mice.
Journal: Biochemical and biophysical research communications20090529
Title: Gateways to clinical trials.
Journal: Methods and findings in experimental and clinical pharmacology20090301
Title: Committed neuronal precursors confer astrocytic potential on residual neural precursor cells.
Journal: Developmental cell20090201
Title: Requirement of Notch activation during regeneration of the intestinal epithelia.
Journal: American journal of physiology. Gastrointestinal and liver physiology20090101
Title: Recent developments in Alzheimer's disease therapeutics.
Journal: BMC medicine20090101
Title: A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.
Journal: PloS one20090101
Title: Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
Journal: Journal of medicinal chemistry20081211
Title: Dynamics of Abeta turnover and deposition in different beta-amyloid precursor protein transgenic mouse models following gamma-secretase inhibition.
Journal: The Journal of pharmacology and experimental therapeutics20081101
Title: Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells.
Journal: Blood20080901
Title: Molecule of the month. Semagacestat.
Journal: Drug news & perspectives20080901
Title: Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease.
Journal: Archives of neurology20080801
Title: A multigram chemical synthesis of the gamma-secretase inhibitor LY411575 and its diastereoisomers.
Journal: Bioorganic & medicinal chemistry letters20071115
Title: Novel orally active, dibenzazepinone-based gamma-secretase inhibitors.
Journal: Bioorganic & medicinal chemistry letters20071101
Title: Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations.
Journal: The Journal of biological chemistry20070824
Title: Dominance of amyloid precursor protein sequence over host cell secretases in determining beta-amyloid profiles studies of interspecies variation and drug action by internally standardized immunoprecipitation/mass spectrometry.
Journal: The Journal of pharmacology and experimental therapeutics20070301
Title: Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-beta after inhibition of gamma-secretase.
Journal: Clinical neuropharmacology20070101
Title: Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse.
Journal: The Journal of pharmacology and experimental therapeutics20061201
Title: Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139.
Journal: The Journal of pharmacology and experimental therapeutics20061101
Title: [The molecular mechanism of Notch-induced transformation and the therapeutic potential of its inhibitor].
Journal: [Rinsho ketsueki] The Japanese journal of clinical hematology20060701
Title: Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease.
Journal: Neurology20060227
Title: Quantitative measurement of changes in amyloid-beta(40) in the rat brain and cerebrospinal fluid following treatment with the gamma-secretase inhibitor LY-411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide].
Journal: The Journal of pharmacology and experimental therapeutics20050501
Title: Lack of specific amyloid-beta(1-42) suppression by nonsteroidal anti-inflammatory drugs in young, plaque-free Tg2576 mice and in guinea pig neuronal cultures.
Journal: The Journal of pharmacology and experimental therapeutics20050101
Title: Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers.
Journal: Clinical neuropharmacology20050101
Title: Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575).
Journal: The Journal of pharmacology and experimental therapeutics20040401
Title: Mitani Y, et al. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci. 2012 Feb 8;32(6):2037-50.
Title: Elvang AB, et al. Differential effects of gamma-secretase and BACE1 inhibition on brain Abeta levels in vitro and in vivo. J Neurochem. 2009 Sep;110(5):1377-87.
Title: Justice NJ, et al. Posttraumatic stress disorder-like induction elevates β-amyloid levels, which directly activates corticotropin-releasing factor neurons to exacerbate stress responses. J Neurosci. 2015 Feb 11;35(6):2612-23.
Title: Portelius E, et al. Acute effect on the Aβ isoform pattern in CSF in response to γ-secretase modulator and inhibitor treatment in dogs. J Alzheimers Dis. 2010;21(3):1005-12.
Title: Junki Hirano, et al. Characterization of SPP inhibitors suppressing propagation of HCV and protozoa. Proc Natl Acad Sci U S A. 2017 Dec12;114(50):E10782-E10791.
