7-oxa[2.2.1]bicycloheptane-2,3-dicarboxylic acid derivatives as phosphatase inhibitors

被引：20

作者：

Enz, A ^{[1
]}

Zenke, G ^{[1
]}

PomboVillar, E ^{[1
]}

机构：

[1] NOVARTIS PHARMA LTD,CH-4002 BASEL,SWITZERLAND

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 19期

关键词：

D O I：

10.1016/S0960-894X(97)10005-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cantharidin (1) as well as norcantharidin or endothall (2) have been described to be inhibitors of protein phosphatase 2A, but were reported to be inactive as inhibitors of calcineurin. Using an HPLC-assay, we have discovered that 1 and 2 are inhibitors of calcineurin-dependent (appKi = 10.8 and 3.26 mu M,respectively) dephosphorylation of a phosphopeptide derived from the RII subunit of c-AMP dependent kinase, HDLDVPIPGRFDRRVS(PO,)VAAE-OH (7), which is commonly used in calcineurin assays. The phosphatase inhibitor 6 also inhibits the production of IL-2 in Jurkat cells, a calcineurin dependent process, with IC50 = 4.7 mu M, indicating that some of the biological activity of this substance class may be due to calcineurin inhibition, in addition to the established PP2A inhibition. (C) 1997 Elsevier Science Ltd.

引用

页码：2513 / 2518

页数：6

共 32 条

[1]

BAUMANN G, 1992, TRANSPLANT P, V24, P43

[2]

BLUMENTHAL DK, 1985, J BIOL CHEM, V261, P6140

[3]

CLEMENTI G, 1994, LIFE SCI, V54, P119

[4] SIMPLE GRAPHICAL METHOD FOR DETERMINING INHIBITION CONSTANTS OF MIXED, UNCOMPETITIVE AND NON-COMPETITIVE INHIBITORS [J].