XL413 (monohydrochloride)

XL413 (BMS-863233) hydrochloride is a potent, selective and ATP competitive inhibitor of Cdc7, with an IC₅₀ of 3.4 nM, and also shows potent effect with IC₅₀s of 215, 42 nM on CK2, PIM1, respectively, and an EC₅₀ of 118 nM on pMCM. IC50 & Target:IC50: 3.4 nM (Cdc7), 42 nM (PIM1), 215 nM (CK2)^[1]
EC50: 118 nM (pMCM)^[1] In Vitro: XL413 (BMS-863233) hydrochloride inhibits the cell proliferation (IC₅₀=2685 nM), decreases cell viability (IC₅₀=2142 nM) and elicits the caspase 3/7 activity (EC₅₀=2288 nM) in Colo-205 cells. XL413 hydrochloride also significantly inhibits the anchorage-independent growth of colo-205 in soft agar (IC₅₀=715 nM)^[1].
XL413 hydrochloride shows cytotoxic effects on tumors, with IC₅₀ of 22.9 µM in HCC1954 cells and 1.1 µM in Colo-205 cells. XL413 hydrochloride induces apoptosis in the Colo-205 cells, but not in HCC1954 cells. XL413 is effective DDK inhibitors in vitro, with IC₅₀ of 22.7 nM. XL413 hydrochloride is defective in inhibiting DDK-dependent Mcm2 phosphorylation in HCC1954 cells but is effective in Colo-205 cells^[2]. In Vivo: XL413 (BMS-863233; 100 mg/kg, p.o.) hydrochloride shows excellent plasma exposures in mice and possesses good PK properties. XL413 (10, 30, or 100 mg/kg, p.o.) hydrochloride is well tolerated at all the doses, with no significant body weight loss^[1].