1422438-59-2Relevant academic research and scientific papers
Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors
Hu, Huiyong,Wang, Xiaojing,Chan, Grace Ka Yan,Chang, Jae H.,Do, Steven,Drummond, Jake,Ebens, Allen,Lee, Wendy,Ly, Justin,Lyssikatos, Joseph P.,Murray, Jeremy,Moffat, John G.,Chao, Qi,Tsui, Vickie,Wallweber, Heidi,Kolesnikov, Aleksandr
, p. 5258 - 5264 (2015)
Pim kinase inhibitors are promising cancer therapeutics. Pim-2, among the three Pim isoforms, plays a critical role in multiple myeloma yet inhibition of Pim-2 is challenging due to its high affinity for ATP. A co-crystal structure of a screening hit 1 bound to Pim-1 kinase revealed the key binding interactions of its indazole core within the ATP binding site. Screening of analogous core fragments afforded 1H-pyrazolo[3,4-c]pyridine (6-azaindazole) as a core for the development of pan-Pim inhibitors. Fragment and structure based drug design led to identification of the series with picomolar biochemical potency against all three Pim isoforms. Desirable cellular potency was also achieved.
