Carboranes Increase the Potency of Small Molecule Inhibitors of Nicotinamide Phosphoribosyltranferase

被引：41

作者：

Lee, Mark W., Jr. ^{[1
]}

Sevryugina, Yulia V. ^{[1
]}

Khan, Aslam ^{[1
]}

Ye, Shui Q. ^{[2
,3
]}

机构：

[1] Univ Missouri, Dept Chem & Radiol, Columbia, MO 65211 USA

[2] Univ Missouri, Childrens Mercy Hosp & Clin, Sch Med, Dept Pediat, Kansas City, MO 64108 USA

[3] Univ Missouri, Childrens Mercy Hosp & Clin, Sch Med, Dept Biomed & Hlth Informat, Kansas City, MO 64108 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 16期

关键词：

D O I：

10.1021/jm300740t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we report the use of carboranes to significantly increase the potency of small molecule inhibitors of nicotinamide phosphoribosyltranferase (Nampt), an enzyme that is central to metabolism and cell survival. We compare the inclusion of carborane with other similarly sized substituents and demonstrate that, compared with their purely organic counterparts, these molecules exhibit up to 10-fold greater antiproliferative activity against cancer cells in vitro and a 100-fold increase in Nampt inhibition.

引用

页码：7290 / 7294

页数：5

共 22 条

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