TY - JOUR
TI - Discovery of novel phenoxazinone derivatives as DKK1/LRP6 interaction inhibitors: Synthesis, biological evaluation and structure-activity relationships
AU - Thysiadis, S.
AU - Mpousis, S.
AU - Avramidis, N.
AU - Katsamakas, S.
AU - Balomenos, A.
AU - Remelli, R.
AU - Efthimiopoulos, S.
AU - Sarli, V.
JO - BIOORGANIC AND MEDICINAL CHEMISTRY
PY - 2016
VL - 24
TODO - 5
SP - 1014-1022
PB - Elsevier Ireland Ltd
SN - 0968-0896
TODO - 10.1016/j.bmc.2016.01.025
TODO - beta catenin;  butyl 7 (dimethylamino) 4 hydroxy 2 [(4 methoxybenzyl) amino] 3 oxo 3h phenoxazine 1 carboxylate;  dickkopf 1 protein;  gallocyanine;  gallocyanine derivative;  low density lipoprotein receptor related protein 6;  methyl 2 (cyclohexylamino) 7 (dimethylamino) 4 hydroxy 3 oxo 3h phenoxazine 1 carboxylate;  methyl 2 (cyclopentylamino) 7 (dimethylamino) 4 hydroxy 3 oxo 3h phenoxazine 1 carboxylate;  methyl 2 amino 7 (dimethylamino) 4 hydroxy 3 oxo 3h phenoxazine 1 carboxylate;  methyl 2 [(3,4 dichlorophenyl)amino] 7 (dimethylamino) 4 hydroxy 3 oxo 3h phenoxazine 1 carboxylate;  methyl 7 (dimethylamino) 4 hydroxy 2 morpholino 3 oxo 3h phenoxazine 1 carboxylate;  methyl 7 (dimethylamino) 4 hydroxy 2 [(4 methoxybenzyl) amino] 3 oxo 3h phenoxazine 1 carboxylate;  methyl 7 (dimethylamino) 4 hydroxy 2 [(4 methoxyphenyl) amino] 3 oxo 3h phenoxazine 1 carboxylate;  methyl 7 (dimethylamino) 4 hydroxy 3 oxo 2 (2 tolyl amino) 3h phenoxazine 1 carboxylate;  methyl 7 (dimethylamino) 4 hydroxy 3 oxo 2 (phenylamino) 3h phenoxazine 1 carboxylate;  methyl 7 (dimethylamino) 4 hydroxy 3 oxo 2 (piperidin 1 yl) 3h phenoxazine 1 carboxylate;  phenoxazinone derivative;  protein inhibitor;  serine;  tau protein;  unclassified drug;  Wnt protein;  DKK1 protein, human;  low density lipoprotein receptor related protein 6;  LRP6 protein, human;  oxazine derivative;  phenoxazinone;  signal peptide, Article;  controlled study;  cytotoxicity;  drug screening;  drug synthesis;  human;  human cell;  protein phosphorylation;  signal transduction;  structure activity relation;  chemistry;  drug effects;  HEK293 cell line;  metabolism;  molecular model;  phosphorylation;  protein protein interaction;  structure activity relation;  synthesis, beta Catenin;  HEK293 Cells;  Humans;  Intercellular Signaling Peptides and Proteins;  Low Density Lipoprotein Receptor-Related Protein-6;  Models, Molecular;  Oxazines;  Phosphorylation;  Protein Interaction Maps;  Signal Transduction;  Structure-Activity Relationship;  Wnt Proteins
TODO - Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of β-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396. © 2016 Elsevier Ltd. All rights reserved.
ER -