184582-62-5Relevant academic research and scientific papers
ACRIDINES AS INHIBITORS OF HASPIN AND DYRK KINASES
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, (2011/10/31)
The present disclosure is directed to compounds of Formula I: which are inhibitors of Haspin kinase and DYRK kinases. The compounds of the present disclosure, and compositions thereof, are useful in the treatment of disease related to Haspin kinase and DY
Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors
Cuny, Gregory D.,Robin, Maxime,Ulyanova, Natalia P.,Patnaik, Debasis,Pique, Valerie,Casano, Gilles,Liu, Ji-Feng,Lin, Xiangjie,Xian, Jun,Glicksman, Marcie A.,Stein, Ross L.,Higgins, Jonathan M.G.
scheme or table, p. 3491 - 3494 (2010/08/21)
Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure-activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC50 50 400 nM) with a 5.4-fold selectivity over haspin was also identified.
