CCT244747
Based on 5 publication(s) in Google Scholar
CCT244747 is a potent, orally bioavailable and highly selective CHK1 inhibitor, with an IC50 of 7.7 nM; CCT244747 also abrogates G2 checkpoint with an IC50 of 29 nM.
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- 純度: 99.46%
- CAS 番号: 1404095-34-6
- 分子式: C20H24N8O2
- 分子量:408.46
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
MedChemExpress（MCE）の使用を引用している文献 CCT244747
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生物活性
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Chk1 7.7 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| HEK293 | IC50 |
5 μM
Compound: 26, CCT244747
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Inhibition of human ERG overexpressed in HEK cells
Inhibition of human ERG overexpressed in HEK cells
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[PMID: 23082860] |
| HT-29 | IC50 |
29 nM
Compound: 26, CCT244747
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Inhibition of CHK1 in human HT-29 cells assessed as etoposide-induced G2 check point arrest after 21 hrs by ELISA
Inhibition of CHK1 in human HT-29 cells assessed as etoposide-induced G2 check point arrest after 21 hrs by ELISA
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[PMID: 23082860] |
CCT244747 poorly inhibits CHK2 (IC50 >10 μM) and CDK1 (IC50 >10 μM). CCT244747 has potent activities against CHK1, RSK1, RSK2, AMPK, BRSK1, IRAK1,and TrkA, with >80% inhibition. CCT244747 (10 μM) exhibits <25% inhibition of the other ion channels including hNav1.5, hKv4.3/hKChIP2, hCav1.2, hKv1.5, hKCNQ1/hminK, hHCN4[1]. CCT244747 inhibits FLT3 with an IC50 of 600 nM. CCT244747 (0.5 μM) overcomes genotoxic-induced S and G2 cell cycle arrest in human colon cancer cell lines. CCT244747 inhibits cellular CHK1 function with IC50s ranging from 29 nM to 170 nM for cellular G2 checkpoint abrogation (MIA, mitosis induction assay) in HT29, SW620, MiaPaCa-2, and Calu6 cell lines; the GI50s are between 0.33 and 3μM. CCT244747 (0.3 μM) inhibits SN38 and gemcitabine-induced CHK1 activity in HT29 and SW620 colon cancer cell lines and this correlates with abrogation of cell cycle arrest, induction of DNA damage and apoptosis[2]. CCT244747 (0.5-2.0 μM) increases the sensitivity of bladder and head and neck cancer cell lines (T24, RT112 and Cal27) to radiation[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
化学情報
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CAS 番号 1404095-34-6
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性状 Solid
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分子量 408.46
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分子式 C20H24N8O2
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Color Light yellow to yellow
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SMILES
N#CC1=NC=C(NC2=NC=C(C3=CN(C)N=C3)C(OC)=C2)N=C1O[C@H](C)CN(C)C
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (5)
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Journal Impact Factor
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Most Recent
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Nat Commun
Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]2026 Feb 12;17(1):1214. PMID: 41680175 -
Nat Commun
Genotoxic stress and viral infection induce transient expression of APOBEC3A and pro-inflammatory genes through two distinct pathways. [Abstract]2021 Aug 13;12(1):4917. PMID: 34389714 -
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溶剤 & 溶解度
DMSO : 50 mg/mL (122.41 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.12 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
CHK1 kinase activity is measured in a microfluidic assay that monitored the separation of a phosphorylated product from its substrate. The assay is run on an EZ Reader II using separation buffer containing CR-8 (500 nM). An ECHO® 550 acoustic dispenser is used to generate duplicate 8 pt dilution curves directly into 384 polypropylene assay plates. For each compound a 50 μM stock concentration in 100% DMSO is used. The total amount of DMSO dispensed per well is 250 nL to give a final assay concentration of 2.5% DMSO and compound concentrations in the range 0.5-1000 nM. To this assay plate, 6 PL CHK1 (2 nM final concentration, in-house protein preparation), 2 PL peptide 10 (5-FAM-KKKVSRSGLYRSPSMPENLNRPR-COOH, 1.5 PM final concentration) and 2 PL ATP (90 PM final concentration) all diluted in kinase buffer (HEPES 50 mM, NaN3 0.02%, BSA 0.01%, sodium orthovanadate 0.1 mM, DTT 1 mM, MgCl2 2 mM, Tween20 0.1%) are added. The plate is sealed and centrifuged (1 min, 1000 rpm) before ncubation for 1 h at room temperature. The reaction is stopped by the addition of separation buffer (90 PL). The plate is read on an EZ Reader II, using a 12-sipper chip with instrument settings of -1.5 psi and 1750 ΔV. The percentage conversion of product from substrate is generated automatically and the percentage inhibition is calculated relative to blank wells (containing no enzyme and 2.5% DMSO) and total wells (containing all reagents and 2.5% DMSO). IC50 values are calculated in GraphPad Prism5 using a non linear regression fit of the log (inhibitor) vs response with variable slope equation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Compound cytotoxicity and the ability of CHK1 inhibitors to enhance SN38 (the active metabolite of the topoisomerase I inhibitor irinotecan) and gemcitabine (an antimetabolite) cytotoxicity is assessed using a 96 h sulforhodamine B assay (SRB). HT29 or SW620 cells are seeded at 1.6 to 3.2 × 103 cells per well in 96-well plates in a volume of 160 μL medium and allowed to attach for 36 h prior to treatment. For cytotoxicity assays, CHK1 inhibitors (10 mM stock in DMSO) are serially diluted in medium from a starting concentration of 250 PM and then 40 PL is added to appropriate wells in quadruplicate to give a final concentration range of 50-0.1 PM (10 concentrations). Genotoxic agents (SN38; 10 mM stock in DMSO) are serially diluted in medium from a starting concentration of 2 PM and 40 PL is added to each well inquadruplicate to give final concentrations from 200-0.39 nM (10 concentrations). Cells are incubated for 96 h (four doublings) at 37°C in a humidified 5% CO2 environment and then fixed and stained with SRB. Appropriate controls are included and results are expressed as the concentration of test compound required to inhibit cell growth by 50% relative to untreated controls (SRB IC50). Potentiation assays involved adding a fixed SRB IC50 concentration of either gemcitabine or SN38 in a volume of 20 μL of medium (10× final concentration), to each well in quadruplicate and mixing for 1 min. CHK1 inhibitor (10 mM stock) is serially diluted from a starting concentration of 50 PM in medium and 20 PL is added per well in quadruplicate to give a final concentration range of 5-0.039 PM (8 concentrations). After mixing for 1 min the cells are incubated at 37°C in a humidified atmosphere for 96 h (four doublings) prior to fixing and SRB staining. Untreated and genotoxic alone treated controls are included and results are expressed as the concentration of CHK1 inhibitor required to inhibit cell growth by 50% (potentiation IC50). The potentiation index (PI) is used as a measure of the ability of the CHK1 inhibitor to enhance SN38 or gemcitabine cytotoxicity and is the ratio of the SRB IC50 versus potentiation IC50 (PI = SRB IC50 / Potentiation IC50)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Female BALB/c mice (6 weeks old) are kept in a controlled environment with food and sterilized water available ad libitum. Animals weighed 20 (±2) g at the time of experiment. Dosing solutions are prepared by dissolving the compounds in 10% DMSO and 5% Tween20 in 85% saline. The compounds are administered i.v. and p.o., individually. Animals are warmed before receiving a single i.v. bolus injection into a lateral tail vein. Oral administration is by oral gavage. Blood is collected at selected time points (1 h and 6 h after dosing) by cardiac puncture under anesthesia into heparinized syringes, transferred to micro centrifuge tubes, and centrifuged at 4500 × g for 2 min to obtain plasma. Quantitative analysis is performed by high performance liquid chromatography tandem mass spectrometry on a triple quadrupole instrument using multiple reaction monitoring of selected transitions with olomoucine used as internal standard. Quantitation is performed against a standard curve ranging from concentrations of 2-1000 nM in the matrix measured. Quality controls are included at the level of 25, 250 and 750 nM. If required, samples are diluted in the matrix of interest[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
純度とドキュメンテーション
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データシート (281 KB)
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SDS (643 KB)
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- Portuguese - PT (643 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Lainchbury M, et al. Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. J Med Chem. 2012 Nov 26;55(22):10229-40. [Content Brief]
[2]. Walton MI, et al. CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs. Clin Cancer Res. 2012 Oct 15;18(20):5650-61. [Content Brief]
[3]. Patel R, et al. An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation. Radiother Oncol. 2017 Mar;122(3):470-475. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4482 mL | 12.2411 mL | 24.4822 mL | 61.2055 mL |
| 5 mM | 0.4896 mL | 2.4482 mL | 4.8964 mL | 12.2411 mL | |
| 10 mM | 0.2448 mL | 1.2241 mL | 2.4482 mL | 6.1206 mL | |
| 15 mM | 0.1632 mL | 0.8161 mL | 1.6321 mL | 4.0804 mL | |
| 20 mM | 0.1224 mL | 0.6121 mL | 1.2241 mL | 3.0603 mL | |
| 25 mM | 0.0979 mL | 0.4896 mL | 0.9793 mL | 2.4482 mL | |
| 30 mM | 0.0816 mL | 0.4080 mL | 0.8161 mL | 2.0402 mL | |
| 40 mM | 0.0612 mL | 0.3060 mL | 0.6121 mL | 1.5301 mL | |
| 50 mM | 0.0490 mL | 0.2448 mL | 0.4896 mL | 1.2241 mL | |
| 60 mM | 0.0408 mL | 0.2040 mL | 0.4080 mL | 1.0201 mL | |
| 80 mM | 0.0306 mL | 0.1530 mL | 0.3060 mL | 0.7651 mL | |
| 100 mM | 0.0245 mL | 0.1224 mL | 0.2448 mL | 0.6121 mL |
CCT244747 関連分類
HY-18175 関連分類
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