1. BIIB042, a novel γ-secretase modulator, reduces amyloidogenic Aβ isoforms in primates and rodents and plaque pathology in a mouse model of Alzheimer's disease.

    Neuropharmacology 103:57 (2016) PMID 26690893

    Reducing the production of larger aggregation-prone amyloid β-peptides (Aβ) remains an untested therapeutic approach for reducing the appearance and growth of Aβ plaques in the brain, which are a hallmark pathological feature of Alzheimer's disease. γ-Secretase modulators (GSMs) are therapeutics...
  2. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway.

    Journal of Pharmacology and Experimental Therap... 341(1):274 (2012) PMID 22267202

    Oxidative stress is central to the pathology of several neurodegenerative diseases, including multiple sclerosis, and therapeutics designed to enhance antioxidant potential could have clinical value. The objective of this study was to characterize the potential direct neuroprotective effects of ...
  3. Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach.

    Bioorganic & Medicinal Chemistry Letters 21(24):7277 (2011) PMID 22061640

    Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to...
  4. Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator.

    ACS Medicinal Chemistry Letters 2(10):786 (2011) PMID 24900267 PMCID PMC4018072

    We have investigated a novel series of acid-derived γ-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent γ-secretase modulator, w...
  5. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway.

    Brain 134(Pt 3):678 (2011) PMID 21354971

    Inflammation and oxidative stress are thought to promote tissue damage in multiple sclerosis. Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for multiple sclerosis treatment. BG00012 is an oral formulation of dimethylfumarate. In a phase II multiple sc...
  6. Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs.

    Bioorganic & Medicinal Chemistry Letters 20(7):2264 (2010) PMID 20188554 PMCID PMC2843818

    Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (-)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified ...