(S)-N-(5-Chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol a Notch-1-sparing gamma-secretase inhibitor.
Bioorg Med Chem Lett
; 19(3): 926-9, 2009 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-19097890
ABSTRACT
Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (Abeta(40/42) EC(50)=28 nM), which is efficacious in reduction of Abeta production in vivo.
Full text:
1
Database:
MEDLINE
Main subject:
Receptor, Notch1
/
Amyloid Precursor Protein Secretases
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Alzheimer Disease
/
Isoleucine
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2009
Type:
Article
Affiliation country:
United States