کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1398898 | 1501130 | 2014 | 10 صفحه PDF | دانلود رایگان |
• MCR based drug discovery led to the identification of two tractable RET leads.
• From kinetic binding and modeling studies, data suggests compounds are Type-II inhibitors.
• Two lead compounds were found to inhibit RET activity in vivo.
From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC). Structure activity relationship studies (SAR) identified two sub-micromolar tractable leads, 6g and 13g. 6g was confirmed to be a Type-II RET inhibitor. 13g and 6g inhibited RET in cells transformed by RET/C634. A RET DFG-out homology model was established and utilized to predict Type-II inhibitor binding modes.
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Journal: European Journal of Medicinal Chemistry - Volume 86, 30 October 2014, Pages 714–723