XL413 (BMS-863233) HCl

Alias: XL413; BMS863233; XL-413; BMS-863233; XL 413; BMS 863233

Cat No.:V1543 Purity: ≥98%

COA Product Data Instructions for use SDS

XL413 HCl (XL-413; BMS863233; XL 413; BMS-863233), the hydrochloride salt of XL413, is a novel and selective cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antitumor activity.

XL413 (BMS-863233) HCl Chemical Structure CAS No.: 1169562-71-3
Product category: CDK

This product is for research use only, not for human use. We do not sell to patients.

Size	Price	Stock	Qty
5mg
10mg
25mg
50mg
100mg
250mg
500mg
Other Sizes

ADD TO CART CHECKOUT BULK INQUIRY

1-708-310-1919 sales@invivochem.com

Other Forms of XL413 (BMS-863233) HCl:

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

XL413 HCl (XL-413; BMS863233; XL 413; BMS-863233), the hydrochloride salt of XL413, is a novel and selective cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antitumor activity. It exhibits 63-, 12-, and 35-fold selectivity over CK2, Pim-1, and pMCM2, respectively, and inhibits CDC7 with an IC50 of 3.4 nM.

Biological Activity I Assay Protocols (From Reference)

Targets

Cdc7 (IC50 = 3.4 nM); PIM1 (IC50 = 42 nM); CK2 (IC50 = 215 nM)

ln Vitro

XL413 (BMS-863233) hydrochloride causes caspase 3/7 activity (EC50=2288 nM) and suppresses cell proliferation (IC50=2685 nM) in Colo-205 cells while also decreasing cell viability (IC50=2142 nM). The anchorage-independent growth of colo-205 in soft agar is likewise markedly inhibited by XL413 hydrochloride (IC50=715 nM)[1].
XL413 hydrochloride possesses cytotoxic properties against tumors, with an IC50 of 1.1 µM in Colo-205 cells and 22.9 µM in HCC1954 cells. Colo-205 cells undergo apoptosis when exposed to XL413 hydrochloride, but HCC1954 cells do not. With an IC50 of 22.7 nM, XL413 is an effective DDK inhibitor in vitro. In HCC1954 cells, XL413 hydrochloride fails to prevent DDK-dependent Mcm2 phosphorylation, but it works well in Colo-205 cells[2].

ln Vivo

XL413 (BMS-863233; 100 mg/kg, p.o.) hydrochloride exhibits good PK characteristics and excellent plasma exposures in mice. At all dosages, XL413 (10, 30, or 100 mg/kg, p.o.) hydrochloride is well tolerated and does not cause appreciable weight loss[1].

Enzyme Assay

For five minutes, 20 ng of purified human DDK is pre-incubated with DDK inhibitors at escalating concentrations. Next, in a buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl₂, and 1 mM DTT, 10 µCi (γ)-³²P ATP and 1.5 µM cold ATP are added, and the mixture is incubated for 30 minutes at 30°C. The proteins are autoradiographed on HyBlot CL film and SDS-PAGEd after being denatured in 1X Laemmli buffer at 100°C. DDK's auto-phosphorylation is a measure of its kinase activity. Using ImageJ, ³²P-labeled bands are quantified, and GraphPad is used to compute the IC50 values.

Cell Assay

There are 2500 cells plated in each well of 96-well plates used for assays. Cells undergo treatment with small molecule inhibitors after 24 hours, and they are then incubated at 37°C for 72 hours. Next, the cells undergo lysis, and the CellTiter-Glo assay is employed to quantify the ATP content, which serves as a marker of metabolically active cells. Utilizing GraphPad software, IC50 values are determined. 100,000 cells are plated per well in six-well plates used for assays. Small molecule inhibitors are applied to the cells after a day, and they are then cultured for different lengths of time. Trypsinized cells are suspended in 5 milliliters of phosphate-buffered saline. After mixing 30 µL of this suspension with 30 µL of CellTiter-Glo reagent, it is incubated at room temperature for 10 minutes. The EnVision 2104 Multilabel Reader and the BioTek Synergy Neo Microplate Reader are used to measure luminosity.

Animal Protocol

3, 100 mg/kg

Colo-205 xenograft model

References

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

[2]. 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.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C14H13CL2N3O2

Molecular Weight

326.18

Exact Mass

289.06

Elemental Analysis

C, 58.04; H, 4.17; Cl, 12.24; N, 14.50; O, 11.04

CAS #

1169562-71-3

Related CAS #

XL413 monohydrochloride;2062200-97-7;XL413;1169558-38-6

Appearance

solid powder

SMILES

C1C[C@H](NC1)C2=NC3=C(C(=O)N2)OC4=C3C=C(C=C4)Cl.Cl

InChi Key

UNDKJUKLBNARIZ-FVGYRXGTSA-N

InChi Code

InChI=1S/C14H12ClN3O2.ClH/c15-7-3-4-10-8(6-7)11-12(20-10)14(19)18-13(17-11)9-2-1-5-16-9;/h3-4,6,9,16H,1-2,5H2,(H,17,18,19);1H/t9-;/m0./s1

Chemical Name

8-chloro-2-[(2S)-pyrrolidin-2-yl]-3H-[1]benzofuro[3,2-d]pyrimidin-4-one;hydrochloride

Synonyms

XL413; BMS863233; XL-413; BMS-863233; XL 413; BMS 863233

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: <1 mg/mL

Water: ~46 mg/mL (~141.0 mM)

Ethanol: <1 mg/mL

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0658 mL	15.3290 mL	30.6579 mL
	5 mM	0.6132 mL	3.0658 mL	6.1316 mL
	10 mM	0.3066 mL	1.5329 mL	3.0658 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Calculate Reset

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculate Reset

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Calculate Reset

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate Reset

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculate Reset

Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

Two DDK inhibitors, PHA-767491 and XL413, exhibit differential activity against cultured tumor cells. PLoS One . 2014 Nov 20;9(11):e113300.
PHA-767491 and XL413 are similarly effective DDK inhibitors in vitro. PLoS One . 2014 Nov 20;9(11):e113300.
XL413 is defective in inhibiting DDK-dependent Mcm2 phosphorylation in HCC1954 cells but is effective in Colo-205 cells. PLoS One . 2014 Nov 20;9(11):e113300.