Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369134 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
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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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
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,