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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Acta+Pharmacol+Sin
2013 ; 34
(11
): 1397-402
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gab.com Text
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English Wikipedia
Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein
4 in vitro and lowers the blood glucose level in db/db mice
#MMPMID24077632
Cai HY
; Wang T
; Zhao JC
; Sun P
; Yan GR
; Ding HP
; Li YX
; Wang HY
; Zhu WL
; Chen KX
Acta Pharmacol Sin
2013[Nov]; 34
(11
): 1397-402
PMID24077632
show ga
AIM: Fatty acid-binding protein 4 (FABP4) plays an important role in maintaining
glucose and lipid homeostasis. The aim of this study was to find new inhibitors
of FABP4 for the treatment of type 2 diabetes. METHODS: Human FABP4 protein was
expressed, and its inhibitors were detected in 1,8-ANS displacement assay. The
effect of the inhibitor on lipolysis activity was examined in mouse 3T3-L1
preadipocytes. The db/db mice were used to evaluate the anti-diabetic activity of
the inhibitor. Molecular docking and site-directed mutagenesis studies were
carried out to explore the binding mode between the inhibitor and FABP4. RESULTS:
From 232 compounds tested, benzbromarone (BBR), an old uricosuric drug, was
discovered to be the best inhibitor of FABP4 with an IC50 value of 14.8 ?mol/L.
Furthermore, BBR (25 ?mol/L) significantly inhibited forskolin-stimulated
lipolysis in 3T3-L1 cells. Oral administration of BBR (25 or 50 mg/kg, for 4
weeks) dose-dependently reduced the blood glucose level and improved glucose
tolerance and insulin resistance in db/db mice. Molecular docking revealed that
the residues Ser55, Asp76, and Arg126 of FABP4 formed important interactions with
BBR, which was confirmed by site-directed mutagenesis studies. CONCLUSION: BBR is
an inhibitor of FABP4 and a potential drug candidate for the treatment of type 2
diabetes and atherosclerosis.