Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24900386
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24900386
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 ACS+Med+Chem+Lett
2012 ; 3
(10
): 828-33
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Structure-activity relationships for side chain oxysterol agonists of the
hedgehog signaling pathway
#MMPMID24900386
Corman A
; DeBerardinis AM
; Hadden MK
ACS Med Chem Lett
2012[Oct]; 3
(10
): 828-33
PMID24900386
show ga
Oxysterols (OHCs) are byproducts of cholesterol oxidation that are known to
activate the Hedeghog (Hh) signaling pathway. While OHCs that incorporate
hydroxyl groups throughout the scaffold are known, those that act as agonists of
Hh signaling primarily contain a single hydroxyl on the alkyl side chain. We
sought to further explore how side chain hydroxylation patterns affect
oxysterol-mediated Hh activation, by performing a structure-activity relationship
study on a series of synthetic OHCs. The most active analogue, 23(R)-OHC (35),
demonstrated potent activation of Hh signaling in two Hh-dependent cell lines
(EC50 values 0.54-0.65 ?M). In addition, OHC 35 was approximately 3-fold
selective for the Hh pathway as compared to the liver X receptor, a nuclear
receptor that is also activated by endogenous OHCs. Finally, 35 induced
osteogenic differentiation and osteoblast formation in cultured cells, indicating
functional agonism of the Hh pathway.