idoxifene and Gaucher-Disease

idoxifene has been researched along with Gaucher-Disease* in 1 studies

Other Studies

1 other study(ies) available for idoxifene and Gaucher-Disease

Article	Year
Novel compounds that reverse the disease phenotype in Type 2 Gaucher disease patient-derived cells. Bioorganic & medicinal chemistry letters, 2020, 01-15, Volume: 30, Issue:2 Gaucher disease (GD) results from inherited mutations in the lysosomal enzyme β-glucocerobrosidase (GCase). Currently available treatment options for Type 1 GD are not efficacious for treating neuronopathic Type 2 and 3 GD due to their inability to cross the blood-brain barrier. In an effort to identify small molecules which could be optimized for CNS penetration we identified tamoxifen from a high throughput phenotypic screen on Type 2 GD patient-derived fibroblasts which reversed the disease phenotype. Structure activity studies around this scaffold led to novel molecules that displayed improved potency, efficacy and reduced estrogenic/antiestrogenic activity compared to the original hits. Here we present the design, synthesis and structure activity relationships that led to the lead molecule Compound 31. Topics: Cells, Cultured; Fibroblasts; Gaucher Disease; Glucosylceramidase; Humans; Inhibitory Concentration 50; Lysosomes; Phenotype; Small Molecule Libraries; Structure-Activity Relationship; Tamoxifen	2020

Article

Year

Novel compounds that reverse the disease phenotype in Type 2 Gaucher disease patient-derived cells.

Bioorganic & medicinal chemistry letters, 2020, 01-15, Volume: 30, Issue:2

Gaucher disease (GD) results from inherited mutations in the lysosomal enzyme β-glucocerobrosidase (GCase). Currently available treatment options for Type 1 GD are not efficacious for treating neuronopathic Type 2 and 3 GD due to their inability to cross the blood-brain barrier. In an effort to identify small molecules which could be optimized for CNS penetration we identified tamoxifen from a high throughput phenotypic screen on Type 2 GD patient-derived fibroblasts which reversed the disease phenotype. Structure activity studies around this scaffold led to novel molecules that displayed improved potency, efficacy and reduced estrogenic/antiestrogenic activity compared to the original hits. Here we present the design, synthesis and structure activity relationships that led to the lead molecule Compound 31.

Topics: Cells, Cultured; Fibroblasts; Gaucher Disease; Glucosylceramidase; Humans; Inhibitory Concentration 50; Lysosomes; Phenotype; Small Molecule Libraries; Structure-Activity Relationship; Tamoxifen

2020