"目录号: HY-15260
Cell Cycle/DNA Damage-
XL413是高活性Cdc7抑制剂，IC50为3.7 nM，比对CK2，PIM和其余100种蛋白激酶的抑制性高60倍，10倍和300倍以上。
CDK
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生物活性
Description
XL413 is a potent and selective Cdc7 inhibitor with an IC50 of 3.7 nM, >60-fold selectivity against CK2, >10-fold selectivity against PIM, and >300-fold selectivity against a panel of over 100 protein kinases.IC50 value: 3.7 nM [1]Target: Selective Cdc 7XL413 demonstrated excellent plasma exposures in mice [100 mg/kg (PO): 141 lM (1 h), 81 lM (4 h)]. Prolonged treatment with XL413 (3 days) inhibited the cell proliferation (IC50 = 2685 nM), decreased cell viability (IC50 = 2142 nM) and elicited the caspase 3/7 activity (EC50 = 2288 nM) in Colo-205 cells.XL413 demonstrated an excellent exposure profile infull rat PK assay (dosed at 3 mg/kg: Cmax (PO) = 8.61 lM, AUC(po) = 75 lM h, CL = 117 mL/h kg, Vss = 0.55 L/kg, T1/2 = 2.32 h, F = 95%). Tumor bearing mice were administered XL413 orally at doses of 10, 30, or 100 mg/kg once daily (qd) for 14 days,XL413 was well tolerated at all the doses and regimens examined, with no significant body weight loss observed [1].
References
[1].Stephenson R, et al. Characterization of a Drosophila Ortholog of the Cdc7 Kinase: A Role for Cdc7 in Endoreplication Independent of Chiffon. J Biol Chem. 2014 Dec 1. pii: jbc.M114.597948.
[2].Sasi NK, et al. The Potent Cdc7-Dbf4 (DDK) Kinase Inhibitor XL413 Has Limited Activity in Many Cancer Cell Lines and Discovery of Potential New DDK Inhibitor Scaffolds. PLoS One. 2014 Nov 20;9(11):e113300.
[3].Koltun ES, et al. Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31.