Discovery of a Highly Selective STK16 Kinase Inhibitor

STK16, a serine/threonine protein
kinase, is ubiquitously expressed and is conserved among all eukaryotes.
STK16 has been implicated to function in a variety of cellular processes
such as VEGF and cargo secretion, but the pathways through which these
effects are mediated remain to be elucidated. Through screening of
our focused library of kinase inhibitors, we discovered a highly selective
ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory
activity against STK16 kinase (IC50: 0.295 μM) with
excellent selectivity across the kinome as assessed using the KinomeScan
profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with
STK16-IN-1 results in a reduction in cell number and accumulation
of binucleated cells, which can be recapitulated by RNAi knockdown
of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as
cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight
potentiation of the antiproliferative effects of the chemotherapeutics.
STK16-IN-1 provides a useful tool compound for further elucidating
the biological functions of STK16.