%0 Journal Article %1 Kumar.2009 %A Kumar, R. %A Crouthamel, M. C. %A Rominger, D. H. %A Gontarek, R. R. %A Tummino, P. J. %A Levin, R. A. %A King, A. G. %D 2009 %J Br.J.Cancer %K & 3 50 Angiogenesis Benzenesulfonates Bone Cell Cells Concentration Diseases Endothelial Factor Growth Hematologic Hematopoietic Human Humans Indoles Inhibitors Inhibitory Kinase Line Marrow Myelopoiesis Phosphorylation Platelet-Derived Protein Proteins Proto-Oncogene Pyridines Pyrimidines Pyrroles Receptors Research Specificity Stem Substrate Sulfonamides Tumor Tyrosine Vascular antagonists c-kit chemically drug effects enzymology fms-Like induced inhibitors methods pharmacology protein %N 10 %P 1717-1723 %T Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors %U PM:19844230 %V 101 %X BACKGROUND: Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. METHODS: Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. RESULTS: Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopan

@article{Kumar.2009, abstract = {BACKGROUND: Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. METHODS: Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. RESULTS: Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopan}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Kumar, R. and Crouthamel, M. C. and Rominger, D. H. and Gontarek, R. R. and Tummino, P. J. and Levin, R. A. and King, A. G.}, biburl = {https://www.bibsonomy.org/bibtex/2da3316c6e820f72389299eecdae161d6/kanefendt}, interhash = {1f2ad4d49884ed85da86aa093426c60d}, intrahash = {da3316c6e820f72389299eecdae161d6}, journal = {Br.J.Cancer}, keywords = {& 3 50 Angiogenesis Benzenesulfonates Bone Cell Cells Concentration Diseases Endothelial Factor Growth Hematologic Hematopoietic Human Humans Indoles Inhibitors Inhibitory Kinase Line Marrow Myelopoiesis Phosphorylation Platelet-Derived Protein Proteins Proto-Oncogene Pyridines Pyrimidines Pyrroles Receptors Research Specificity Stem Substrate Sulfonamides Tumor Tyrosine Vascular antagonists c-kit chemically drug effects enzymology fms-Like induced inhibitors methods pharmacology protein}, number = 10, pages = {1717-1723}, timestamp = {2010-02-05T11:28:51.000+0100}, title = {Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors}, url = {PM:19844230}, volume = 101, year = 2009 }