Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in 
mitosis that has emerged as a possible cancer therapeutic target. High 
throughput screening of approximately 140,000 compounds identified the 
beta-carbolines harmine and harmol as moderately potent haspin kinase 
inhibitors. Based on information obtained from a structure-activity relationship 
study previously conducted for an acridine series of haspin inhibitors in 
conjunction with in silico docking using a recently disclosed crystal structure 
of the kinase, harmine analogs were designed that resulted in significantly 
increased haspin kinase inhibitory potency. The harmine derivatives also 
demonstrated less activity towards DYRK2 compared to the acridine series. In 
vitro mouse liver microsome stability and kinase profiling of a representative 
member of the harmine series (42, LDN-211898) are also presented.