sotrastaurin and Graft-vs-Host-Disease

The PKC-θ isoform of protein kinase C is selectively expressed in T lymphocytes and plays an important role in the T cell antigen receptor (TCR)-triggered activation of mature T cells, T cell proliferation, and the subsequent release of cytokines such as interleukin-2 (IL-2). Herein, we report the synthesis and structure-activity relationship (SAR) of a novel series of PKC-θ inhibitors. Through a combination of structure-guided design and exploratory SAR, suitable replacements for the basic C4 amine of the original lead (

Topics: Animals; Caco-2 Cells; Cell Proliferation; Cyclohexanols; Graft vs Host Disease; Humans; Immunologic Factors; Lymphocyte Activation; Male; Mice, Inbred C57BL; Molecular Docking Simulation; Molecular Structure; Protein Binding; Protein Kinase C-delta; Protein Kinase C-theta; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship; T-Lymphocytes

Topics: Animals; Graft Rejection; Graft vs Host Disease; Humans; Immunosuppression Therapy; Isoenzymes; Mice; Mice, Knockout; Molecular Targeted Therapy; NF-kappa B; Protein Kinase C; Protein Kinase C-theta; Protein Kinase Inhibitors; Psoriasis; Pyrroles; Quinazolines; Signal Transduction; T-Lymphocytes