SEN1500, a novel oral amyloid-β aggregation inhibitor, attenuates brain pathology in a mouse model of Alzheimer's disease.

Introduction: Amyloid-β (Aβ) aggregation is thought to be a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The development of new drugs inhibiting the Aβ aggregation process is, therefore, important. SEN1500, an orally bioavailable and CNS-penetrant Aβ aggregation inhibitor, has previously been shown to reduce spatial learning and memory deficits in an APP transgenic mouse model.

Novel 5-aryloxypyrimidine SEN1576 as a candidate for the treatment of Alzheimer's disease.

Prefibrillar assembly of amyloid-β (Aβ) is a major event underlying the development of neuropathology and dementia in Alzheimer's disease (AD). This study determined the neuroprotective properties of an orally bioavailable Aβ synaptotoxicity inhibitor, SEN1576. Binding of SEN1576 to monomeric Aβ 1-42 was measured using surface plasmon resonance.

Dose-dependent improvements in learning and memory deficits in APPPS1-21 transgenic mice treated with the orally active Aβ toxicity inhibitor SEN1500.

In the Alzheimer's disease (AD) brain, accumulation of Aβ1-42 peptides is suggested to initiate a cascade of pathological events. To date, no treatments are available that can reverse or delay AD-related symptoms in patients. In the current study, we introduce a new Aβ toxicity inhibitor, SEN1500, which in addition to its block effect on Aβ1-42 toxicity in synaptophysin assays, can be administered orally and cross the blood-brain barrier without adverse effects in mice.

AβPP-overexpressing transgenic rat model of Alzheimer's disease utilizing the Tg2576 mouse protocol.

The current study examined behavioral and histological effects of amyloid-β (Aβ) protein precursor (AβPP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg+ rats were bred with female wild-type rats to generate litters of hemizygous Tg+ and Tg- offspring. Tg+ rats and Tg- littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure.

Orally bioavailable small molecule drug protects memory in Alzheimer's disease models.

Oligomers of beta-amyloid (Aβ) are implicated in the early memory impairment seen in Alzheimer's disease before to the onset of discernable neurodegeneration. Here, the capacity of a novel orally bioavailable, central nervous system-penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived (7PA2 [conditioned medium] CM) Aβ-induced deficits in synaptic plasticity and learned behavior was assessed. Biochemically, SEN1500 bound to Aβ monomer and oligomers, produced a reduction in thioflavin-T fluorescence, and protected a neuronal cell line and primary cortical neurons exposed to synthetic soluble oligomeric Aβ(1-42).