XL413 HYDROCHLORIDE

XL413 inhibits the cell proliferation (IC ₅₀ = 2685 nM), decreases cell viability (IC ₅₀ = 2142 nM) and elicits the caspase 3/7 activity (EC ₅₀ = 2288 nM) in Colo-205 cells. XL413 also significantly inhibits the anchorage-independent growth of colo-205 in soft agar (IC ₅₀ = 715 nM). XL413 shows cytotoxic effects on tumors, with IC ₅₀ of 22.9 µM in HCC1954 cells and 1.1 µM in Colo-205 cells. XL413 induces apoptosis in the Colo-205 cells, but not in HCC1954 cells. XL413 is effective DDK inhibitors in vitro, with IC ₅₀ of 22.7 nM. XL413 is defective in inhibiting DDK-dependent Mcm2 phosphorylation in HCC1954 cells but is effective in Colo-205 cells.

XL413 (100 mg/kg, p.o.) shows excellent plasma exposures in mice and possesses good PK properties. XL413 (10, 30, or 100 mg/kg, p.o.) is well tolerated at all the doses, with no significant body weight loss.