The first two cantharidin analogues displaying PP1 selectivity

Adam McCluskey; Mirella A Keane; Cecilia C Walkom; Michael C Bowyer; Alistair T R Sim; David J Young; Jennette A Sakoff

doi:10.1016/s0960-894x(01)00777-6

The first two cantharidin analogues displaying PP1 selectivity

Bioorg Med Chem Lett. 2002 Feb 11;12(3):391-3. doi: 10.1016/s0960-894x(01)00777-6.

Authors

Adam McCluskey¹, Mirella A Keane, Cecilia C Walkom, Michael C Bowyer, Alistair T R Sim, David J Young, Jennette A Sakoff

Affiliation

¹ Medicinal Chemistry Group, School of Biological and Chemical Sciences, The University of Newcastle, University Drive, Callaghan, Newcastle, NSW 2308, Australia. amcclusk@mail.newcastle.edu.au

PMID: 11814804
DOI: 10.1016/s0960-894x(01)00777-6

Abstract

High pressure Diels-Alder reactions of furan and dimethylmaleate, and thiophene and maleimide resulted in two cantharidin analogues, 3 and 6 possessing PP1 selectivity (>40- and >30-fold selectivity) over PP2A. Both compounds exhibited moderate PP1 activity, 3 IC(50) 50 microM and 6 IC(50) 12.5 microM. Interestingly, the corresponding mono-ester derivatives of 3 showed no such selectivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cantharidin / analogs & derivatives*
Cantharidin / chemical synthesis
Cantharidin / pharmacology*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Indicators and Reagents
Phosphoprotein Phosphatases / antagonists & inhibitors*
Structure-Activity Relationship
Substrate Specificity

Substances

Enzyme Inhibitors
Indicators and Reagents
Phosphoprotein Phosphatases
Cantharidin