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| Targets |
CCT251455 targets monopolar spindle 1 (MPS1/TTK), a protein kinase that is essential for the spindle assembly checkpoint (SAC). The SAC is a surveillance mechanism that ensures all chromosomes are correctly attached to the mitotic spindle before anaphase. By inhibiting MPS1, CCT251455 forces cells to proceed through mitosis with unattached or incorrectly attached chromosomes, leading to aneuploidy and cell death. This makes it a promising target for cancer therapy.
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| ln Vitro |
In comparison to kinases examined in a wide kinome analysis panel, CCT251455 is a highly potent MPS1 inhibitor with high selectivity. A cell-based assay [1] shows that CCT251455 inhibits P-MPS1 with an IC50 of 0.04 μM and a GI50 of 0.16 μM.
In vitro, CCT251455 is a highly potent inhibitor of MPS1 with an IC50 of 3 nM. It demonstrates high selectivity versus kinases tested in a broad kinome profiling panel. In cell-based assays, it inhibits P-MPS1 with an IC50 of 0.04 μM and has a GI50 of 0.16 μM against HCT116 colon cancer cells. These results confirm its potent cellular activity and selectivity. |
| ln Vivo |
Following oral treatment, CCT251455 suppresses MPS1 activity in vivo and demonstrates favorable oral pharmacokinetic properties in mice and rats [1].
In vivo, CCT251455 suppresses MPS1 activity following oral treatment and demonstrates favorable oral pharmacokinetic properties in mice and rats. Its in vivo efficacy has been evaluated in xenograft models, where it has shown antitumor activity. The compound's oral bioavailability supports its development as a therapeutic agent for cancer. |
| Enzyme Assay |
The in vitro activity of CCT251455 against MPS1 is determined using cell-free kinase assays. In these assays, the MPS1 enzyme is incubated with a substrate and ATP in the presence or absence of the compound. The phosphorylation of the substrate is then measured, and the IC50 is calculated. This assay provides a direct measure of the compound's potency against its primary target.
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| Cell Assay |
The in vitro cellular activity of CCT251455 is assessed in cell-based assays measuring MPS1 activity and cell proliferation. Cells are treated with the compound, and the phosphorylation of MPS1 substrates (P-MPS1) is measured to confirm target engagement. Cell proliferation is assessed using standard assays, and the GI50 is calculated. The compound's ability to induce mitotic defects can also be visualized by microscopy.
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| Animal Protocol |
The in vivo efficacy of CCT251455 is evaluated in xenograft mouse models. Human tumor cells are implanted into immunodeficient mice. When tumors reach a certain size, the animals are treated with CCT251455 via oral gavage. Tumor growth is monitored, and at the end of the study, tumors are analyzed for markers of MPS1 inhibition. These studies confirm its in vivo antitumor activity.
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| ADME/Pharmacokinetics |
Dosing in animal models is typically oral, as CCT251455 is orally bioavailable. The compound is formulated in a suitable vehicle for oral administration. Pharmacokinetic studies in mice and rats have demonstrated favorable oral pharmacokinetic properties.
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| Toxicity/Toxicokinetics |
The safety and toxicity of CCT251455 would be assessed in standard preclinical toxicology studies. As an inhibitor of the spindle assembly checkpoint, its toxicity profile is related to its effect on mitosis in rapidly dividing cells. These studies are essential for determining its therapeutic index and identifying any potential adverse effects.
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| References | |
| Additional Infomation |
CCT251455 is a potent and selective inhibitor of MPS1/TTK with an IC50 of 3 nM. It disrupts the spindle assembly checkpoint, leading to mitotic catastrophe and cell death. It has favorable oral pharmacokinetic properties and has shown preclinical antitumor activity. It is a research compound being investigated for its potential as an anticancer agent, but it is not an approved drug.
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| Molecular Formula |
C26H26CLN7O2
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|---|---|
| Molecular Weight |
503.98
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| Exact Mass |
503.183
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| CAS # |
1400284-80-1
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| PubChem CID |
66547425
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| Appearance |
Light yellow to brown solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
731.0±70.0 °C at 760 mmHg
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| Flash Point |
395.9±35.7 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.674
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| LogP |
5.54
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
782
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BXKNUXDLZJPPBO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H26ClN7O2/c1-26(2,3)36-25(35)34-21(18-12-30-33(5)14-18)9-17-11-29-24(10-22(17)34)31-20-7-6-16(8-19(20)27)23-13-28-15-32(23)4/h6-15H,1-5H3,(H,29,31)
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| Chemical Name |
tert-butyl 6-[2-chloro-4-(3-methylimidazol-4-yl)anilino]-2-(1-methylpyrazol-4-yl)pyrrolo[3,2-c]pyridine-1-carboxylate
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| Synonyms |
CCT 251455; CCT-251455; CCT251455
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~198.42 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.96 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 (4.96 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (4.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9842 mL | 9.9210 mL | 19.8421 mL | |
| 5 mM | 0.3968 mL | 1.9842 mL | 3.9684 mL | |
| 10 mM | 0.1984 mL | 0.9921 mL | 1.9842 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.
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.
(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.
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