Famotidine inhibits glycogen synthase kinase-3β: An investigation by docking simulation and experimental validation

被引：8

作者：

Mohammad, Mohammad ^{[1
]}

Al-Masri, Ihab M. ^{[2
]}

Issa, Ala ^{[1
]}

Al-Ghussein, Mohamed A. S. ^{[2
]}

Fararjeh, Mohammad ^{[3
]}

Alkhatib, Hatim ^{[1
]}

Taha, Mutasem O. ^{[1
]}

Bustanji, Yasser ^{[1
]}

机构：

[1] Univ Jordan, Fac Pharm, Amman 11942, Jordan

[2] Al Azhar Univ, Fac Pharm, Gaza, Gaza Strip, Jordan

[3] Hashemite Univ, Fac Allied Hlth Sci, Zarqa, Jordan

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2013年 / 28卷 / 04期

关键词：

Famotidine; glycogen synthase kinase; docking simulation; H2-receptor antagonist; GLUCOSE-TOLERANCE; CIMETIDINE; INSULIN; DISEASE; KINASE;

D O I：

10.3109/14756366.2012.672413

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Famotidine was investigated as an inhibitor of glycogen synthase kinase-3 beta (GSK-3 beta) in an attempt to explain the molecular mechanism of its hypoglycemic side effects. The investigation included simulated docking experiments, in vitro enzyme inhibition assay, glycogen sparing studies using animal models and single dose oral glucose tolerance test (OGTT). Docking studies showed how famotidine is optimally fit within the binding pocket of GSK-3 beta via numerous attractive interactions with some specific amino acids. Experimentally, famotidine could inhibit GSK-3 beta (IC50 = 1.44 mu M) and increased significantly liver glycogen spares in fasting animal models. Moreover, a single oral dose of famotidine was shown to decrease the glycemic response curve after 75 g OGTT

引用

页码：690 / 694

页数：5

共 17 条

[11] First non-ATP competitive glycogen synthase kinase 3 β (GSK-3β) inhibitors:: Thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease [J].