Abstract 3905: Synthesis and structure activity relationship of substituted N,6-diphenyl-5,6-dihydrobenzo[h]quinazolin-2-amine as inhibitors of fibroblast growth factor receptors (FGFR)
| العنوان: | Abstract 3905: Synthesis and structure activity relationship of substituted N,6-diphenyl-5,6-dihydrobenzo[h]quinazolin-2-amine as inhibitors of fibroblast growth factor receptors (FGFR) |
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| المؤلفون: | Syed M. Ali, Chris Brassard, Audra Dalton, Darin Kizer, Jean-Marc Lapierre, Yanbin Liu, Magdi Moussa, Rocio Palma, Manish Tandon, David Vensel, Erika Volckova, Jianqiang Wang, Neil Westlund, Hui Wu, Rui-Yang Yang, Craig Bates, Mayank Bhavsar, Cathy Bull, Sudharshan Eathiraj, Robert Nicewonger, Ron Savage, Carol Waghorne, Jennifer Castro, Enkeleda Nakuci, Chang-Rung Chen, Dennis S. France, Thomas C.K. Chan, Mark A. Ashwell |
| المصدر: | Cancer Research. 72:3905-3905 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, Kinase, In silico, Cancer, Pharmacology, Biology, medicine.disease, In vitro, Oncology, Biochemistry, In vivo, Fibroblast growth factor receptor, medicine, Structure–activity relationship, Tyrosine kinase |
| الوصف: | Utilization of hydrophobic motifs present in auto-inhibited protein kinases has resulted in the identification of a series of 5,6-dihydrobenzo [h]quinazolin-2-amines with activity as fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors. Herein we describe the combination of a proprietary in silico design process, a new screening paradigm using an array of biochemical and biophysical technologies in conjunction with an established parallel chemistry process for the identification and optimization of a series of novel FGFR inhibitors. These potent FGFR inhibitors exhibit a preference for the inactive form of the kinase, are non-ATP competitive, and exhibit robust cellular pharmacodynamic inhibition as well as in vitro anti-proliferative effects in cells dependent on FGFR and significant anti-tumor activity in appropriate xenograft models in vivo. The design strategy, synthesis, structure activity relationships and in vitro and in vivo biology of selected inhibitors will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3905. doi:1538-7445.AM2012-3905 |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::f3f2f570d6e9677ed33340d22c18292f https://doi.org/10.1158/1538-7445.am2012-3905 |
| رقم الأكسشن: | edsair.doi...........f3f2f570d6e9677ed33340d22c18292f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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