کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1369134 | 981764 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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![عکس صفحه اول مقاله: Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design](/preview/png/1369134.png)
چکیده انگلیسی
Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 11, 1 June 2013, Pages 3149–3153
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 11, 1 June 2013, Pages 3149–3153
نویسندگان
Xiaojing Wang, Steven Magnuson, Rich Pastor, Eric Fan, Huiyong Hu, Vickie Tsui, Wei Deng, Jeremy Murray, Micah Steffek, Heidi Wallweber, John Moffat, Jason Drummond, Grace Chan, Eric Harstad, Allen J. Ebens,