کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1359823 981417 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-based drug design identifies novel LPA3 antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure-based drug design identifies novel LPA3 antagonists
چکیده انگلیسی

Compound 5 ([5-(3-nitrophenoxy)-1,3-dioxo-1,3-dihydro-2-isoindol-2-yl]acetic acid) was identified as a weak selective LPA3 antagonist (IC50 = 4504 nM) in a virtual screening effort to optimize a dual LPA2 and 3 antagonist. Structure-based drug design techniques were used to prioritize similarity search matches of compound 5. This strategy rapidly identified 10 novel antagonists. The two most efficacious compounds identified inhibit activation of the LPA3 receptor by 200 nM LPA with IC50 values of 752 nM and 2992 nM. These compounds additionally define changes to our previously reported pharmacophore that will improve its ability to identify more potent and selective LPA3 receptor antagonists. The results of the combined computational and experimental screening are reported.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 21, 1 November 2009, Pages 7457–7464
نویسندگان
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