| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Cot inhibitor-2 targets the COT/Tpl2 (MAP3K8) kinase, a key regulator of the inflammatory response. It is a potent inhibitor with an IC50 of 1.6 nM. By inhibiting COT/Tpl2, it modulates the MAPK signaling pathway, which is crucial for the production of pro-inflammatory cytokines, particularly TNF-α. This makes it a promising candidate for treating inflammatory diseases such as rheumatoid arthritis.
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| ln Vitro |
In vitro, Cot inhibitor-2 demonstrates potent inhibitory activity. It inhibits COT/Tpl2 kinase activity with an IC50 of 1.6 nM. In functional assays using LPS-stimulated human whole blood, it inhibits TNF-α production with an IC50 of 0.3 μM. Its high potency and selectivity make it a valuable tool for dissecting the role of COT/Tpl2 in various cellular contexts.
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| ln Vivo |
At a dosage of 100 mg/kg, Cot Inhibitor-2 (Compound 34) had a Cmax of 517 ng/mL (0.89 μM) and an AUC of 4841 ng h/mL. In a paradigm where LPS causes TNF-α production in female Sprague-Dawley rats, Cot inhibitor-2 was evaluated. Cot inhibitor-2 inhibits LPS-induced TNF-α by 83% at an injury dose of 25 mg/kg [1].
In vivo, Cot inhibitor-2 is used as a research tool to study the role of COT/Tpl2 in inflammatory diseases. Its oral bioavailability allows for convenient administration in animal models. By inhibiting TNF-α production, it has the potential to alleviate inflammation in conditions such as rheumatoid arthritis and cancer. It is used to validate COT/Tpl2 as a therapeutic target and to explore its role in disease pathogenesis. |
| Enzyme Assay |
The in vitro kinase assay for Cot inhibitor-2 involves measuring its ability to inhibit the phosphorylation activity of COT/Tpl2 (MAP3K8). The enzyme is incubated with a peptide substrate and ATP in the presence of varying concentrations of the compound. The amount of phosphorylated substrate is measured using a luminescent or fluorescent detection system, and the IC50 is calculated from the dose-response curve. The compound's selectivity is confirmed by testing it against a panel of other kinases.
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| Cell Assay |
In vitro cell-based assays for Cot inhibitor-2 utilize LPS-stimulated human whole blood or peripheral blood mononuclear cells (PBMCs). Cells are treated with the compound and stimulated with LPS to induce an inflammatory response. The production of TNF-α and other cytokines is measured by ELISA. The compound's ability to inhibit TNF-α production is quantified, and the IC50 is calculated from the dose-response curve.
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| Animal Protocol |
Cot inhibitor-2 is a solid compound with a molecular weight of 539.43 g/mol. It is soluble in DMSO at ≥100 mg/mL (185.38 mM). For in vivo studies, it can be formulated in suitable vehicles such as PEG300 or corn oil. It is typically stored at -20°C, with stock solutions stable for up to 6 months at -80°C and 1 month at -20°C.
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| ADME/Pharmacokinetics |
Toxicological data for Cot inhibitor-2 are limited, as it is a research compound not intended for human use. Comprehensive toxicity studies have not been reported. Standard safety precautions for handling chemical reagents should be followed. Its potent inhibition of TNF-α production suggests it could have significant immunomodulatory effects.
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| Toxicity/Toxicokinetics |
Cot inhibitor-2 is a research compound with no clinical approval. It is a valuable tool for studying COT/Tpl2 biology and the role of MAPK signaling in inflammation. It is used in drug discovery programs to explore the therapeutic potential of COT/Tpl2 inhibitors for the treatment of inflammatory diseases, including rheumatoid arthritis and cancer.
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| References | |
| Additional Infomation |
8-Chloro-4-(3-Chloro-4-fluoroaniline)-6-[[1-(1-ethyl-4-piperidinyl)-4-triazolyl]methylamino]-3-quinoline nitrile is an aminoquinoline.
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| Molecular Formula |
C26H25N8FCL2
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|---|---|
| Molecular Weight |
539.4347
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| Exact Mass |
538.156
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| CAS # |
915363-56-3
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| PubChem CID |
44143370
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| Appearance |
Light yellow to green yellow solid powder
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| Density |
1.45
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| Boiling Point |
713.3ºC at 760 mmHg
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| Flash Point |
385.2ºC
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| Index of Refraction |
1.702
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| LogP |
6.24
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
37
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| Complexity |
792
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PHNZIIMWDVXPGG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H25Cl2FN8/c1-2-36-7-5-20(6-8-36)37-15-19(34-35-37)14-31-18-9-21-25(33-17-3-4-24(29)22(27)10-17)16(12-30)13-32-26(21)23(28)11-18/h3-4,9-11,13,15,20,31H,2,5-8,14H2,1H3,(H,32,33)
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| Chemical Name |
8-chloro-4-(3-chloro-4-fluoroanilino)-6-[[1-(1-ethylpiperidin-4-yl)triazol-4-yl]methylamino]quinoline-3-carbonitrile
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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 : ~40 mg/mL (~74.15 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (5.56 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 30.0 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: ≥ 3 mg/mL (5.56 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 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2 mg/mL (3.71 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8538 mL | 9.2690 mL | 18.5381 mL | |
| 5 mM | 0.3708 mL | 1.8538 mL | 3.7076 mL | |
| 10 mM | 0.1854 mL | 0.9269 mL | 1.8538 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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