KRCA-0008

Alias: KRCA-0008; KRCA0008; KRCA 0008

Cat No.:V23301 Purity: ≥98%

COA Product Data Instructions for use SDS

KRCA-0008 is a novel, potent dual inhibitor of Ack1 and anaplastic lymphoma kinase (ALK)with IC50 of 12 nM/4 nM for ALK and Ack1 respectively; displays drug-like properties without hERG liability.

KRCA-0008 Chemical Structure CAS No.: 1472795-20-2
Product category: ALK

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

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Citations by Top Journals: Nature, Cell, Science, etc.

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.

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators

Product Description

KRCA-0008 exhibits drug-like characteristics without hERG liability. It is a novel, potent dual inhibitor of anaplastic lymphoma kinase (ALK) and Ack1, with IC50 values of 12 nM/4 nM for ALK and Ack1, respectively.

Biological Activity I Assay Protocols (From Reference)

Targets	ALK (IC50 = 12 nM); Ack1 (IC50 = 4 nM)
ln Vitro	With IC50 values of 12, 75, 4, 17, 17, and 17, respectively, KRCA-0008 (0-1000 μM) demonstrated effectiveness against ALK (wt), ALK L1196 M, ALK C1156Y, ALK F1174L, ALK R1275Q, and insulin receptor. More efficiently than crizotinib, KRCA-0008 (0-1000 nM; 4 hours) suppresses ALK-dependent signaling regulation [2]. At 210 nM, KRCA-0008 (0-1000 nM; 72 h) stimulates cells [1]. KRCA-0008 has a 48-hour half-life (0–100 nM) [2].
ln Vivo	The ALK-positive Karpas-299 xenograft model is inhibited in its development by KRCA-0008 (25 and 50 mg/kg; lateral, twice daily, intermittent) [2].
Cell Assay	Cell proliferation analysis [1] Cell Types: H3122 and H1993 cell lines Tested Concentrations: 200 nM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibited cell proliferation of H3122 and H1993 cells with IC50 of 0.08 and 3.6 nM respectively. Cell proliferation assay[2] Cell Types: NPM-ALK positive ALCL cell line (Karpas-299 and SU-DHL-1) and U937 NPM ALK negative lymphoma cell line Tested Concentrations: 200 nM Incubation Duration: 72 hrs (hours) Experimental Results: Proliferation was inhibited The GI50 of Karpas-299, SU-DHL-1 and U937 cells are 12 nM, 3 nM and 3.5 μM respectively. Western Blot Analysis[2] Cell Types: Karpas-299 and SU-DHL-1 Cell Lines Tested Concentrations: 0, 10, 100 and 1000 nM Incubation Duration: 4 hrs (hours) Experimental Results: Complete inhibition of phosphorylation of ALK and its effectors at dose 100 nM in NPM-ALK-positive ALCL cells. Apoptosis analysis[2] Cell Types: SU-DHL-1 Cell line Tested Concentrations: 0-1 μM Incubation Duration: 72 hrs (hours) Experimental Results: cspase-3/7 activity increased in a dose-dependent manner and induced apoptosis. Cell cycle ana
Animal Protocol	Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse with Karpas-299 xenografts [2] Doses: 25 and 50 mg/kg Route of Administration: po (oral gavage); 25 and 50 mg/kg twice (two times) daily; two-week Experimental Results: Dramatically inhibited tumor growth by inhibiting NPM-ALK phosphorylation without exhibiting overt signs of toxicity or significant compound-related weight loss.
References	[1]. Park CH, et al. Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment. Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6. [2]. Hwang J, et al. KRCA-0008 suppresses ALK-positive anaplastic large-cell lymphoma growth. Invest New Drugs. 2020 Oct;38(5):1282-1291.

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

Physicochemical Properties

Molecular Formula	C30H37CLN8O4
Molecular Weight	609.12
Exact Mass	608.2626
Elemental Analysis	C, 59.16; H, 6.12; Cl, 5.82; N, 18.40; O, 10.51
CAS #	1472795-20-2
Related CAS #	1472795-20-2
Appearance	Solid powder
SMILES	CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC(=NC=C3Cl)NC4=C(C=C(C=C4)N5CCN(CC5)C(=O)C)OC)OC
InChi Key	TXDIRJCYNAWBOS-UHFFFAOYSA-N
InChi Code	InChI=1S/C30H37ClN8O4/c1-20(40)36-9-13-38(14-10-36)22-5-7-25(27(17-22)42-3)33-29-24(31)19-32-30(35-29)34-26-8-6-23(18-28(26)43-4)39-15-11-37(12-16-39)21(2)41/h5-8,17-19H,9-16H2,1-4H3,(H2,32,33,34,35)
Chemical Name	1-[4-[4-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]-3-methoxyphenyl]piperazin-1-yl]ethanone
Synonyms	KRCA-0008; KRCA0008; KRCA 0008
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: ~230 mg/mL (~377.6 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 5.75 mg/mL (9.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 5.75 mg/mL (9.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More Solubility in Formulation 3: ≥ 1.25 mg/mL (2.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: ~230 mg/mL (~377.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5.75 mg/mL (9.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 2: ≥ 5.75 mg/mL (9.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

View More

Solubility in Formulation 3: ≥ 1.25 mg/mL (2.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6417 mL	8.2086 mL	16.4171 mL
	5 mM	0.3283 mL	1.6417 mL	3.2834 mL
	10 mM	0.1642 mL	0.8209 mL	1.6417 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

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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
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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.

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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

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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.

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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

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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.)

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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.