Abstract
The indolyl-naphthyl maleimide 7 is a potent inhibitor of the classical PKC isotypes α,β and shows excellent selectivity over the novel PKC isotypes δ,ε,η,θ and other kinases belonging to the AGC family. The SAR around 7 as well as the physico-chemical characteristics of selected derivatives and their activity in T and B cell activation and proliferation assays are discussed.
Keywords:
B-cell activation; Inhibitors; PKC alpha/beta; T-cell activation.
Copyright © 2017 Elsevier Ltd. All rights reserved.
MeSH terms
-
B-Lymphocytes / cytology
-
B-Lymphocytes / drug effects*
-
B-Lymphocytes / metabolism
-
Binding Sites
-
Cell Proliferation / drug effects
-
Humans
-
Indoles / chemistry
-
Inhibitory Concentration 50
-
Isoenzymes / antagonists & inhibitors
-
Isoenzymes / metabolism
-
Lymphocyte Activation / drug effects
-
Maleimides / chemical synthesis
-
Maleimides / chemistry*
-
Maleimides / pharmacology*
-
Molecular Docking Simulation
-
Naphthols / chemistry
-
Protein Binding
-
Protein Kinase C beta / antagonists & inhibitors*
-
Protein Kinase C beta / metabolism
-
Protein Kinase C-alpha / antagonists & inhibitors*
-
Protein Kinase C-alpha / metabolism
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology
-
Protein Structure, Tertiary
-
Structure-Activity Relationship
-
T-Lymphocytes / cytology
-
T-Lymphocytes / drug effects*
-
T-Lymphocytes / metabolism
Substances
-
Indoles
-
Isoenzymes
-
Maleimides
-
Naphthols
-
Protein Kinase Inhibitors
-
Protein Kinase C beta
-
Protein Kinase C-alpha