Isoform-selectivity of PKC inhibitors acting at the regulatory and catalytic domain of mammalian PKC-alpha, -beta I, -delta, -eta and -zeta

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Saraiva, L (Author) FFUP; Fresco, P (Author) FFUP; Pinto, E (Author) FFUP; Goncalves, J (Author) FFUP

Journal

Title: Journal of Enzyme Inhibition and Medicinal Chemistry

Vol. 18

Pages: 475-483

ISSN: 1475-6366

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 20 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-000-E9Z

DOI: 10.1080/14756360310001603158

Abstract (EN): The aim of the present study was to compare the potency of a series of widely used PKC inhibitors acting either at the regulatory (NPC 15437, tamoxifen and d -sphingosine) or at the catalytic domain (Ro 32-0432, chelerythrine and rottlerin) on individual mammalian PKC isoforms of the classical (alpha and betaI), novel (delta and eta) and atypical (zeta) PKC families, using the yeast phenotypic assay, in order to determine their isoform-selectivity. The PKC inhibitors studied presented differences in their ability to reduce the effect of the appropriate PKC activator (estimated as EC50 ratios) which was interpreted as an index of PKC inhibitory potency. In general, the more marked inhibition was observed on novel PKC isoforms, particularly on PKC-eta. This study indicates promising isoform-selectivity of some PKC inhibitors, namely NPC 15437 for PKC-eta or rottlerin for both novel PKC isoforms. It also suggests that the PKC domain involved in the inhibition does not seem to be relevant for the potency and isoform-selectivity of PKC inhibitors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9