1436685-40-3Relevant academic research and scientific papers
Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design
Wang, Xiaojing,Magnuson, Steven,Pastor, Rich,Fan, Eric,Hu, Huiyong,Tsui, Vickie,Deng, Wei,Murray, Jeremy,Steffek, Micah,Wallweber, Heidi,Moffat, John,Drummond, Jason,Chan, Grace,Harstad, Eric,Ebens, Allen J.
, p. 3149 - 3153 (2013/06/27)
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.
