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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

326.18

C₁₄H₁₃Cl₂N₃O₂

2062200-97-7

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

In Vitro: 

H₂O : 10 mg/mL (30.66 mM; Need ultrasonic)

DMSO : 3.4 mg/mL (10.42 mM; Need ultrasonic and warming)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

• [1]. Koltun ES, et al. Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31.

  [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.

20 ng of purified human DDK is pre-incubated with increasing concentrations of each DDK inhibitor for 5 min. Then 10 µCi (γ)-³²P ATP and 1.5 µM cold ATP are added in a buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl₂, and 1 mM DTT and incubated for 30 min at 30°C. The proteins are denatured in 1X Laemmli buffer at 100°C followed by SDS-PAGE and autoradiography on HyBlot CL film. Auto-phosphorylation of DDK is used as an indicator of its kinase activity. ³²P-labeled bands are quantified using ImageJ and the IC₅₀ values are calculated using GraphPad.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

For assays in 96 well plates 2500 cells are plated per well. After 24 hours, cells are treated with small molecule inhibitors and incubated for 72 hours at 37°C. Subsequently the cells are lysed and the ATP content is measured as an indicator of metabolically active cells using the CellTiter-Glo assay. IC₅₀ values are calculated using the GraphPad software. For assays in six well plates, 100,000 cells are plated per well. After 24 hours, cells are treated with small molecule inhibitors and incubated for varying time points. Cells are trypsinized and a suspension is made in 5 mL of phosphate buffered saline. 30 µL of this suspension is mixed with 30 µL of CellTiter-Glo reagent followed by a 10-minute incubation at room temperature. Luminescence is measured using EnVision 2104 Multilabel Reader and BioTek Synergy Neo Microplate Reader.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Koltun ES, et al. Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31.

  [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.