CCT251545 |
| رقم الكتالوجGC17606 |
CCT251545 هو مثبط متاح حيويًا وقويًا عن طريق الفم لإشارات WNT مع IC 50 من 5 نانومتر في 7dF3 خلاياCCT251545 عبارة عن مسبار كيميائي انتقائي لاستكشاف دور CDK8 و CDK19 في الأمراض التي تصيب الإنسان
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Cas No.: 1661839-45-7
Sample solution is provided at 25 µL, 10mM.
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CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with IC50 value of 5 nM [1].
The WNT signaling network controls cellular functions such as proliferation and differentiation, and is a major regulator of mammalian development. WNT signaling is frequently deregulated in malignancy, especially in colon cancer, and plays an important role in the generation and maintenance of cancer stem cells [1].
CCT251545 is an orally bioavailable and potent WNT signaling inhibitor discovered through high-throughput cell-based screening. CCT251545 is also a potent and selective chemical probe for the human Mediator complex-associated protein kinases CDK8 and CDK19. CCT251545 changed gene expression regulated by WNT pathway and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1 [2]. CCT251545 also inhibited GSK3α and -β with IC50 values of 0.462 and 0.690 μM. In APC mutant human colorectal cancer cell line (COLO205-F1756 clone 4), CCT251545 inhibited WNT pathway activity with IC50 value of 0.035 nM [1].
In both mouse and rat, CCT251545 exhibited moderate clearance with moderate to high oral bioavailability. In mice bearing COLO205-F1756 clone 4 tumor xenografts, CCT251545 (70 mg/kg po bid for 9 days) significantly inhibited WNT signaling and reduced tumor weights by 37.5% [1].
References:
[1]. Mallinger A, Crumpler S, Pichowicz M, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem, 2015, 58(4): 1717-1735.
[2]. Dale T, Clarke PA, Esdar C, et al. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol, 2015, 11(12): 973-980.
| Cell experiment [1]: | |
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Cell lines |
APC mutant human colorectal cancer cell line (COLO205-F1756 clone 4) |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.035 μM |
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Applications |
In COLO205-F1756 clone 4, CCT251545 potently inhibited WNT pathway activity, with the IC50 value of 0.035 μM. Moreover, CCT251545 did not affect endogenous levels of TCF1 or TCF4. |
| Animal experiment [1]: | |
|
Animal models |
Mice bearing COLO205-F1756 clone 4 xenografts |
|
Dosage form |
70 mg/kg; p.o.; b.i.d., for 9 days |
|
Applications |
In mice bearing COLO205-F1756 clone 4 xenografts, CCT251545 (70 mg/kg; p.o.; b.i.d., for 9 days) substantially inhibited WNT signaling and reduced tumor weights by 37.5%. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Mallinger A, Crumpler S, Pichowicz M, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem, 2015, 58(4): 1717-1735. | |
| Cas No. | 1661839-45-7 | SDF | |
| Chemical Name | 8-(3-chloro-5-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one | ||
| Canonical SMILES | O=C(NCC1)C1(CC2)CCN2C3=C(C4=CC=C(C5=CN(C)N=C5)C=C4)C=NC=C3Cl | ||
| Formula | C23H24ClN5O | M.Wt | 421.92 |
| الذوبان | ≥ 42.2mg/mL in DMSO | 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 | 2.3701 mL | 11.8506 mL | 23.7012 mL |
| 5 mM | 0.474 mL | 2.3701 mL | 4.7402 mL |
| 10 mM | 0.237 mL | 1.1851 mL | 2.3701 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 25 reference(s) in Google Scholar.)
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