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Chemical Structure| 1261269-01-5 Chemical Structure| 1261269-01-5

Structure of 1261269-01-5

Chemical Structure| 1261269-01-5

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Ganga Reddy Velma ; Megan S. Laham ; Cutler Lewandowski ; Ana C. Valencia-Olvera ; Deebika Balu ; Annabelle Moore , et al.

Abstract: Therapeutics enhancing apolipoprotein (APOE) positive function are a priority, because APOE4 is the major genetic risk factor for Alzheimer’s disease (AD). The function of APOE, the key constituent of lipoprotein particles that transport cholesterol and lipids in the brain, is dependent on lipidation by ABCA1, a cell_x005f_x0002_membrane cholesterol transporter. ABCA1 transcription is regulated by liver X receptors (LXR): agonists have been shown to increase ABCA1, often accompanied by unwanted lipogenesis and elevated triglycerides (TG). Therefore, nonlipogenic ABCA1-inducers (NLAI) are needed. Two rounds of optimization of an HTS hit, derived from a phenotypic screen, gave lead compound 39 that was validated and tested in E3/4FAD mice that express human APOE3/4 and five mutant APP and PSEN1 human transgenes. Treatment with 39 increased ABCA1 expression, enhanced APOE lipidation, and reversed multiple AD phenotypes, without increasing TG. This NLAI/LXR-agonist study is the first in a human APOE-expressing model with hallmark pathology.

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Product Details of [ 1261269-01-5 ]

CAS No. :1261269-01-5
Formula : C9H10ClNO2
M.W : 199.63
SMILES Code : O=C(OCC)C1=CC(Cl)=CC(N)=C1
MDL No. :MFCD17276491

Safety of [ 1261269-01-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P264-P270-P301+P312-P330
 

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