CCT-241533 HCl

Alias: CCT 241533; CCT241533; CCT-241533 HCl; CCT-241533; CCT 241533 dihydrochloride

Cat No.:V5293 Purity: ≥98%

COA Product Data Instructions for use SDS

CCT241533 HCl, the dihydrochloride salt of CCT-241533, is a novel, potent and selective CHK2 inhibitor with anticancer activity.

CCT-241533 HCl Chemical Structure CAS No.: 1431697-96-9
Product category: Chk

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

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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
Clinical Trial Information
Biological Data

Product Description

CCT241533 HCl, the dihydrochloride salt of CCT-241533, is a novel, potent and selective CHK2 inhibitor with anticancer activity. It inhibits CHK2 with an IC50 of 3 nM and a Ki of 1.16 nM. At an IC50 of 3 nM and a Ki of 1.16 nM, it inhibits CHK2. It demonstrates selectivity for Chk1 over Chk2 and a panel of 84 other kinases by >63-fold. Dihydrochloride CCT 241533 inhibits HT29 cells' Chk2 activation in response to etoposide-induced DNA damage and prevents mouse thymocytes from dying when exposed to ionizing radiation.

Biological Activity I Assay Protocols (From Reference)

Targets	Chk2 (IC50 = 3 nM); Chk1 (IC50 = 245 nM); Chk2 (Ki = 1.16 nM)
ln Vitro	CCT241533 hydrochloride exhibits negligible cross-reactivity against a panel of kinases at 1 μM and inhibits CHK2 with an IC50 of 3 nM. The ATP pocket is where CCT241533 binds to CHK2, as confirmed by X-ray crystallography. In response to DNA damage, CCT241533 inhibits CHK2 activity in human tumor cell lines, as evidenced by the suppression of CHK2 autophosphorylation at S516, band-shift mobility changes, and HDMX degradation. In a number of cell lines, CCT241533 does not increase the cytotoxicity of a few genotoxic substances. Nonetheless, the cytotoxicity of two structurally different PARP inhibitors is markedly enhanced by CCT241533. A PARP inhibitor by itself clearly activates the pS516 CHK2 signal, and CCT241533 reverses this activation. According to the growth inhibitory IC50 (GI50) of the SRB assay, the cytotoxicity of CCT241533 in HT-29, HeLa, and MCF-7 is 1.7, 2.2, and 5.1 μM, in that order[1]. Potent CHK2 inhibitor CCT241533 hydrochloride (IC50=3 nM) has low hERG inhibition (IC50=22 μM) and selectivity (63-fold) over CHK1 (IC50=190 nM)[2].
Cell Assay	In a 96-hour SRB assay or a 7–10 day colony forming assay, HT-29, HeLa, and MCF-7 cells are exposed to a fixed concentration (GI50) of CCT241533 in combination with increasing concentrations of either PARP inhibitor or cytotoxic drug. Potentiation index (PI), which is the ratio of GI50 for the genotoxic or PARP inhibitor alone: GI50 for the genotoxic or PARP inhibitor in combination with a CHK2 inhibitor, is used to express CCT241533's capacity to increase cell killing. Consequently, PI<1 denotes protection and PI>1 denotes potentiation[1].
References	[1]. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72. [2]. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.

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

Physicochemical Properties

Molecular Formula	C23H28CLFN4O4
Molecular Weight	478.944228172302
Exact Mass	514.15
Elemental Analysis	C, 53.60; H, 5.67; Cl, 13.76; F, 3.69; N, 10.87; O, 12.42
CAS #	1431697-96-9
Related CAS #	CCT241533 dihydrochloride;1962925-28-5;CCT241533;1262849-73-9
Appearance	Solid powder
SMILES	CC(C)([C@@H]1CNC[C@H]1NC2=NC(=NC3=CC(=C(C=C32)OC)OC)C4=C(C=CC(=C4)F)O)O.Cl
InChi Key	LAKJUTZIXHTMPC-SSPJITILSA-N
InChi Code	InChI=1S/C23H27FN4O4.ClH/c1-23(2,30)15-10-25-11-17(15)27-21-13-8-19(31-3)20(32-4)9-16(13)26-22(28-21)14-7-12(24)5-6-18(14)29;/h5-9,15,17,25,29-30H,10-11H2,1-4H3,(H,26,27,28);1H/t15-,17-;/m1./s1
Chemical Name	4-fluoro-2-[4-[[(3S,4R)-4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl]amino]-6,7-dimethoxyquinazolin-2-yl]phenol;hydrochloride
Synonyms	CCT 241533; CCT241533; CCT-241533 HCl; CCT-241533; CCT 241533 dihydrochloride
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: ≥100 mg/mL (~208.8 mM) H2O: ~33.3 mg/mL (~69.6 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.22 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 25.0 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. View More Solubility in Formulation 3: ≥ 2.5 mg/mL (5.22 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: ≥100 mg/mL (~208.8 mM)
H2O: ~33.3 mg/mL (~69.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 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 25.0 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.

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.22 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 25.0 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.

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.22 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 5: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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.

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0879 mL	10.4397 mL	20.8794 mL
	5 mM	0.4176 mL	2.0879 mL	4.1759 mL
	10 mM	0.2088 mL	1.0440 mL	2.0879 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*

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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
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.

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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

Molecular formula

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g/mol

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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

Average weight of animals g

Dosing volume per animal μL

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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.)

% DMSO

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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.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04177498	Recruiting	Other: Quality-of-Life Assessment Drug: Rigosertib Sodium	Recessive Dystrophic Epidermolysis Bullosa	Thomas Jefferson University	August 24, 2021	Early Phase 1
NCT04263090	Recruiting	Drug: Rigosertib Drug: Nivolumab	Adenocarcinoma Stage IV	Icahn School of Medicine at Mount Sinai	June 29, 2020	Phase 1 Phase 2
NCT03786237	Recruiting	Drug: Rigosertib Oral Capsules / Rigosertib Intravenous	Epidermolysis Bullosa Dystrophica Squamous Cell Carcinoma	Prof. Johann Bauer	April 12, 2021	Phase 1 Phase 2
NCT05764395	Recruiting	Drug: Rigosertib Procedure: Biopsy	Metastatic Melanoma Refractory Melanoma	Vanderbilt-Ingram Cancer Center	May 9, 2023	Phase 2
NCT02030639	Completed	Drug: rigosertib	Healthy	Onconova Therapeutics, Inc.	January 2014	Phase 1

Biological Data

(A) Characterization of the CHK2 activation pathway and p53 status in a panel of human tumor cell lines.Cancer Res.2011 Jan 15;71(2):463-72.
Effect of Bleomycin treatments on CHK2 activation and cell cycle distribution.Cancer Res.2011 Jan 15;71(2):463-72.
(A) Effect of CCT241533 on olaparib cytotoxicity and CHK2 activation in HeLa cells.Cancer Res.2011 Jan 15;71(2):463-72.