Abstract 3231: Identifying high quality, potent and selective pyrimidinylthienopyrrolone inhibitors of ERK1/2 kinase: LY3214996
| العنوان: | Abstract 3231: Identifying high quality, potent and selective pyrimidinylthienopyrrolone inhibitors of ERK1/2 kinase: LY3214996 |
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| المؤلفون: | Karen L. Huss, Mclean Johnathan Alexander, Zhao Gaiying, Robert S. Flack, Andrew J. Dropsey, Xueqian Gong, Michael John Rodriguez, Sajan Joseph, Matthew Whitesell, Lisa Kindler, Jennie L. Walgren, Jason Manro, Ramon V. Tiu, Baohui Zhao, Brian Michael Mathes, Denis J. McCann, Xiu-Juan Yuan, Susan Jaken, Shufen Cai, Bryan D. Anderson, William T. McMillen, Eunice Yuen, Shripad V. Bhagwat, Cortez Guillermo S, Wenjuan Wu |
| المصدر: | Cancer Research. 77:3231-3231 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Cancer Research, Kinase, business.industry, Cancer, Pharmacology, medicine.disease, Oncology, In vivo, medicine, Potency, business, Clinical evaluation, IC50, Human cancer |
| الوصف: | The ERK/MAPK pathway plays a central role in the regulation of critical cellular processes and is activated in more than 30% of human cancers. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. ERK inhibitors have the potential to address resistance caused by ERK reactivation. Herein, a potent, selective small molecule ERK1/2 inhibitor is described. LY3214996 possesses an optimal balance of potency (hERK1 IC50 5 nM, hERK2 IC50 5nM, pRSK IC50 0.43 µM), solubility (FaSSIF solubility at pH 6.5 0.133 µM), PK properties (dog, AUCoral 23800 nM*hr, CL 12.1 mL/min/kg, bioavailability 75.4%), IVTI (TED50 =16 mg/kg pRSK1) and demonstrated significant in vivo efficacy in several human cancer xenograft models. LY3214996 is currently undergoing early clinical evaluation. Citation Format: Gaiying Zhao, William T. McMillen, Shufen Cai, Baohui Zhao, Matthew Whitesell, Wenjuan Wu, Karen Huss, Bryan Anderson, Xiu-Juan Yuan, Susan Jaken, Lisa Kindler, Robert S. Flack, Denis McCann, Brian Mathes, Andrew J. Dropsey, Jennie Walgren, Eunice Yuen, Jason Manro, Xueqian Gong, Guillermo Cortez, Johnathan McLean, Michael J. Rodriguez, Ramon V. Tiu, Shripad V. Bhagwat, Sajan Joseph. Identifying high quality, potent and selective pyrimidinylthienopyrrolone inhibitors of ERK1/2 kinase: LY3214996 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3231. doi:10.1158/1538-7445.AM2017-3231 |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2017-3231 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::1824ca165bb8dc39a5634940817bcacd https://doi.org/10.1158/1538-7445.am2017-3231 |
| رقم الانضمام: | edsair.doi...........1824ca165bb8dc39a5634940817bcacd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/1538-7445.am2017-3231 |