کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10591927 981769 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase β isoform
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase β isoform
چکیده انگلیسی
A series of suitable five-membered heterocyclic alternatives to thiophenes within a thienobenzoxepin class of PI3-kinase (PI3K) inhibitors was discovered. Specific thiazolobenzoxepin 8-substitution was identified that increased selectivity over PI3Kβ. PI3Kβ-sparing compound 27 (PI3Kβ Ki,app/PI3Kα Ki,app = 57) demonstrated dose-dependent knockdown of pAKT, pPRAS40 and pS6RP in vivo as well as differential effects in an in vitro proliferation cell line screen compared to pan PI3K inhibitor GDC-0941. A new structure-based hypothesis for reducing inhibition of the PI3K β isoform while maintaining activity against α, δ and γ isoforms is presented.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 9, 1 May 2013, Pages 2606-2613
نویسندگان
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