Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

• Published in: Leukemia Vol. 30; no. 2; pp. 464 - 472
• Main Authors: Peter, B, Winter, G E, Blatt, K, Bennett, K L, Stefanzl, G, Rix, U, Eisenwort, G, Hadzijusufovic, E, Gridling, M, Dutreix, C, Hoermann, G, Schwaab, J, Radia, D, Roesel, J, Manley, P W, Reiter, A, Superti-Furga, G, Valent, P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2016; Nature Publishing Group
• Subjects: 13/31; 13/89; 631/67/1990/283; 82/16; Adult; Aged; Basophils - drug effects; Basophils - physiology; Cancer Research; Cell interaction; Cell Line, Tumor; Cell Survival - drug effects; Cellular proteins; Critical Care Medicine; Dephosphorylation; Drug therapy; Enzyme inhibitors; Female; Genetic aspects; Health aspects; Hematology; Histamine; Histamine Release - drug effects; Humans; In vivo methods and tests; Intensive; Internal Medicine; Kinases; Leukemia; Leukocytes (basophilic); Lysates; Male; Mast cell disease; Mast cells; Mast Cells - drug effects; Mast Cells - physiology; Mastocytosis; Mastocytosis - drug therapy; Mastocytosis - pathology; Medicine; Medicine & Public Health; Metabolites; Methods; Middle Aged; Molecular targeted therapy; Oncology; original-article; Patient outcomes; Patients; Protein kinase C; Protein Kinase Inhibitors - pharmacology; Proteomics; Proto-Oncogene Proteins c-kit - metabolism; Signs and symptoms; Staurosporine - analogs & derivatives; Staurosporine - pharmacology; Syk protein; Austria

Proteomic-based drug testing is an emerging approach to establish the clinical value and anti-neoplastic potential of multikinase inhibitors. The multikinase inhibitor midostaurin (PKC412) is a promising new agent used to treat patients with advanced systemic mastocytosis (SM). We examined the targe...