Nature reviews. Cancer, Journal Year: 2010, Volume and Issue: 10(2), P. 130 - 137
Published: Jan. 22, 2010
Language: Английский
Nature Chemical Biology, Journal Year: 2008, Volume and Issue: 4(11), P. 682 - 690
Published: Oct. 20, 2008
Language: Английский
Citations
3679
Nature Reviews Drug Discovery, Journal Year: 2006, Volume and Issue: 5(12), P. 993 - 996
Published: Dec. 1, 2006
Language: Английский
Citations
3361
Nature reviews. Cancer, Journal Year: 2007, Volume and Issue: 7(3), P. 169 - 181
Published: Feb. 23, 2007
Language: Английский
Citations
3013
Nature reviews. Cancer, Journal Year: 2008, Volume and Issue: 9(1), P. 28 - 39
Published: Dec. 19, 2008
Language: Английский
Citations
2462
Developmental Cell, Journal Year: 2011, Volume and Issue: 21(2), P. 193 - 215
Published: Aug. 1, 2011
Language: Английский
Citations
2376
Nature Biotechnology, Journal Year: 2008, Volume and Issue: 26(1), P. 127 - 132
Published: Jan. 1, 2008
Language: Английский
Citations
2360
Nature Biotechnology, Journal Year: 2011, Volume and Issue: 29(11), P. 1046 - 1051
Published: Oct. 30, 2011
Language: Английский
Citations
2081
Biochemical Journal, Journal Year: 2010, Volume and Issue: 429(3), P. 403 - 417
Published: July 14, 2010
The p38 MAPK (mitogen-activated protein kinase) signalling pathway allows cells to interpret a wide range of external signals and respond appropriately by generating plethora different biological effects. diversity specificity in cellular outcomes is achieved with an apparently simple linear architecture the pathway, consisting core three kinases acting sequentially. In present review, we dissect molecular mechanisms underlying functions, special emphasis on activation regulation kinases, interplay other pathways nature substrates as source functional diversity. Finally, discuss how genetic mouse models are facilitating identification physiological functions for MAPKs, which may impinge their eventual use therapeutic targets.
Language: Английский
Citations
1546
New England Journal of Medicine, Journal Year: 2005, Volume and Issue: 353(19), P. 2012 - 2024
Published: Nov. 9, 2005
The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response EGFR kinase inhibitors. mechanism responsiveness glioblastomas these inhibitors unknown.
Language: Английский
Citations
1430
International Journal of Cancer, Journal Year: 2010, Volume and Issue: 129(1), P. 245 - 255
Published: Dec. 17, 2010
Angiogenesis, a critical driver of tumor development, is controlled by interconnected signaling pathways. Vascular endothelial growth factor receptor (VEGFR) 2 and tyrosine kinase with immunoglobulin epidermal homology domain play crucial roles in the biology normal vasculature. Regorafenib (BAY 73-4506), novel oral multikinase inhibitor, potently inhibits these cell kinases biochemical cellular phosphorylation assays. Furthermore, regorafenib additional angiogenic (VEGFR1/3, platelet-derived receptor-β fibroblast 1) mutant oncogenic KIT, RET B-RAF. The antiangiogenic effect was demonstrated vivo dynamic contrast-enhanced magnetic resonance imaging. administered once orally at 10 mg/kg significantly decreased extravasation Gadomer vasculature rat GS9L glioblastoma xenografts. In daily (qd)×4 dosing study, pharmacodynamic effects persisted for 48 hr after last correlated inhibition (TGI). A significant reduction microvessel area observed human colorectal xenograft qd×5 30 mg/kg. exhibited potent dose-dependent TGI various preclinical models mice, shrinkages breast MDA-MB-231 renal 786-O carcinoma models. Pharmacodynamic analyses model revealed strong staining proliferation marker Ki-67 phosphorylated extracellular regulated 1/2. These data demonstrate that well-tolerated, active inhibitor distinct target profile may have therapeutic benefit malignancies.
Language: Английский
Citations
1239