•Mps1
is overexpressed in both solid and hematological tumors and genetic or chemical
inhibition suppresses tumor growth.
•Novel
small molecule Mps1 inhibitors have been patented.
•The
lead compounds 1 and 13 inhibit Mps1 kinase enzymatic activity with IC50 values
from 0.356 uM
to 0.809 uM,
and inhibited Mps1-associated cellular functions such as centrosome duplication
and the spindle checkpoint in triple negative breast cancer cells.
•The
most promising analog, compound 13, controls tumor growth without weight loss
when given IP daily for 6 weeks in a Cal-51 TNBC xenograft model
•The
lead molecule is orally bioavailable and brain penetrant
•Preliminary
in vitro efficacy in hematologic malignancy