CCT-251921 |
| Catalog No.GC32741 |
CCT-251921 es un inhibidor de CDK8 potente, selectivo y biodisponible por vÍa oral con una IC50 de 2,3 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1607837-31-9
Sample solution is provided at 25 µL, 10mM.
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CCT-251921 is a potent, selective, and orally bioavailable CDK8 inhibitor with an IC50 of 2.3 nM.
CCT-251921 has acceptable aqueous solubility and demonstrates minimal activity when tested in a panel of 55 receptors, ion channels, and enzymes at 1 μM and in a panel of 279 kinases; weak inhibition of CYPs is observed. CCT-251921 demonstrates potent inhibition of reporter-based readouts measuring basal WNT pathway activity in human cancer cell lines that have constitutively activated WNT pathway signaling: LS174T (β-catenin mutant), SW480 and Colo205 (APC mutant) or PA-1 human teratocarcinoma cells that are WNT ligand dependent[1].
CCT-251921 shows improved oral pharmacokinetics and pharmaceutical properties in order to facilitate further evaluation of CDK8/19 pharmacology and progression into preclinical efficacy and safety studies. In APC-mutant SW620 human colorectal carcinoma xenograft model, CCT-251921 treatment reduces mice tumor weight (54.2%) at day 15. The inhibition of STAT1SER727 phosphorylation is maintained for more than 6 h after the last dose[1].
[1]. Mallinger A, et al. Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016 Feb 11;59(3):1078-101.
Cell experiment: | 7dF3 cells are treated with CCT-251921 ranging in final concentration from 90 μM to 0.3 nM. After 2 h of further incubation, β-oestradiol is added to a final concentration of 10 μM. The cells are incubated and then 25 μL of luciferase reagent is added and mixed. After leaving the plate for 60 min at room temperature, luminescence is read on a plate luminescence reader[1]. |
Animal experiment: | Mice: Animals are dosed orally by gavage every 24 h at 0.1 mL per 10 g body weight. Tumors are measured three times weekly by Vernier calipers and body weights recorded. At the end of the study, animals are culled at intervals: 3 control and 3 treated at 1, 2, 6, and 24 h after the final dose. Heparinized blood is collected by cardiac puncture, spun, and plasma snap frozen for analysis of compound exposure. Tumors are excised, weighed and samples snap frozen for compound quantification and PD analyses. The 30 mg/kg q.d. schedule is well tolerated with no significant body weight loss. Tumor growth is significantly inhibited[1]. |
References: [1]. Mallinger A, et al. Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016 Feb 11;59(3):1078-101. | |
| Cas No. | 1607837-31-9 | SDF | |
| Canonical SMILES | O=C1NCCC12CCN(C3=C(Cl)C(N)=NC=C3C4=CC5=C(N(C)N=C5)C=C4)CC2 | ||
| Formula | C21H23ClN6O | M.Wt | 410.9 |
| Solubility | DMSO : ≥ 28 mg/mL (68.14 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4337 mL | 12.1684 mL | 24.3368 mL |
| 5 mM | 0.4867 mL | 2.4337 mL | 4.8674 mL |
| 10 mM | 0.2434 mL | 1.2168 mL | 2.4337 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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