38778-80-2Relevant articles and documents
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.
, p. 3491 - 3494 (2010)
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.
