TP-5801 is a potent, specific inhibitor of Thirty-eight-negative kinase-1 (TNK1) with IC50 of 1.4 nM, inhibits TNK1-transformed cells. TP-5801is potent IC50 of 10.5 nM against TNK1 in Nano-BRET analysis. TP-5801 (300 nM) shows clear selectvity profile against a panel of 371 kinases in vitro, only 7 other kinases were inhibited by more than 90%. TP-5801 inhibits TNK1-driven cell growth with IC50s of 76.78 and 36.95 nM against Ba/F3 WT TNK1 and AAA mutant cells. TP-5801 inhibits BCR-ABL-driven and IL-3-driven Ba/F3 cell growth with IC50s of 8.5 and 1.2 μM, respectively. TP-5801 (10 mg/kg, daily oral administration) significantly reduced tumor burden in NOD/SCID mice were subcutaneously injected with TNK1-AAA driven Ba/F3-luc cells.
