Tipiracil hydrochloride (MA-1 hydrochloride) is a thymidine phosphorylase inhibitor (TPI). Tipiracil hydrochloride is one of the active components in TAS-102, which is an anticancer drug candidate currently in clinical trials.

Tipiracil has an antiangiogenic effect that also inhibits proliferation of endothelial cells[1]. Tipiracil is a potent inhibitor of thymidine phosphorylase, which is the enzyme that degrades FTD[2].

In vitro kinase inhibition assays: Kinase activity for PI3K isoforms is measured as the percentage of ATP consumed following the kinase reaction using luciferase–luciferin-coupled chemiluminescence, with ATP concentrations approximately equal to the Km for each respective kinase. Kinase reactions are initiated by combining test compounds, ATP and kinase in a 20 μL volume. PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ final enzyme concentrations are 0.5, 8, 20, and 2 nM, respectively. Of note, 0.5 μL dimethyl sulfoxide (DMSO) containing varying concentrations of the test compound is mixed with 10 μL enzyme solution (2×concentration). Kinase reactions are initiated by the addition of 10 μL of liver phosphatidylinositol and ATP solution (2×concentration). Assay concentrations for VPS34, ATP, and phosphatidylinositol are 40 nM, 1 μM, and 5 μM, respectively