Human Pim1 kinase is a serine/threonine protein kinase that plays important 
biological roles in cell survival, apoptosis, proliferation, and 
differentiation. Moreover, Pim1 is up-regulated in various hematopoietic 
malignancies and solid tumors. Thus, Pim1 is an attractive target for cancer 
therapeutics, and there has been growing interest in developing small molecule 
inhibitors for Pim1. Here, we describe the crystal structure of Pim1 in complex 
with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068). 
Our inhibitor exhibits a half maximum inhibitory concentration (IC50) of 123 
(±14) nM and has an unusual binding mode in complex with Pim1 kinase. The 
interactions between SKI-O-068 and the Pim1 active site pocket residue are 
different from those of other scaffold inhibitor-bound structures. The binding 
mode analysis suggests that the SKI-O-068 inhibitor can be improved by 
introducing functional groups that facilitate direct interaction with Lys67, 
which aid in the design of an optimized inhibitor.