2-Allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6- (4-(4-methyl- piperazin-1-yl)phenylamino)-1H-pyra -zolo [3,4-d]pyrimidin-3(2H)-one.
MK 1775 (see structure), a small, selective inhibitor molecule, has been found to be
active against many sarcomas when tested by researchers at Moffitt Cancer Center in Tampa, Fla. Researchers found that MK1775 treatment induces apoptopic cell death in four sarcoma cell lines at clinically relevant doses.
To further prove that inhibition of Wee1 by MK1775 leads to mitotic
cell death in sarcomas cells, the researchers performed additional
studies, including studies on sarcomas related to mutations, such as
with the p53 gene.
They also showed that MK1775 was an active inhibitor of Wee1 regardless
of the p53 mutation status of the tumors in the cell lines tested.
"The
cytotoxic effect of Wee1 inhibition on sarcoma cells appears to be
independent of p53 mutation status following our testing sarcoma cell
lines with different p53 mutations," he said. "All of them were highly
sensitive to MK1775, suggesting that Wee1 inhibition may represent a
novel approach in the treatment of sarcomas."
Researchers concluded that their laboratory tests on sarcoma cell lines
suggest that MK1775 is effective as a monotherapy even in the cell
lines that include p53 wild, p53 null and p53 mutant statuses.
