TPCA-1 |
| Catalog No.GC17621 |
A selective inhibitor of IKK2
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 507475-17-4
Sample solution is provided at 25 µL, 10mM.
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TPCA-1 is a novel, potent, and selective inhibitor of human IKK-2.
Demonstration that IκB kinase 2 (IKK-2) plays a pivotal role in the nuclear factor-κB-regulated production of proinflammatory molecules by stimuli such as tumor necrosis factor (TNF)-α and interleukin (IL)-1 suggests that inhibition of IKK-2 may be beneficial in the treatment of rheumatoid arthritis.
In vitro: Determination of the activity of TPCA-1 against ten selected kinases, COX-1 and COX-2, showed the compound to be ~550-fold selective for IKK-2 versus ten of these enzymes. TPCA-1 inhibits lipopolysaccharide-induced human monocyte production of TNF-α, IL-6, and IL-8 with an IC50 of 170 to 320 nM [1].
In vivo: Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg resulted in a dose dependent reduction in the severity of murine collagen-induced arthritis. The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg were comparable to the effects of the antirheumatic drug, etanercept [1].
Clinical trial: No clinical data are available currently.
Reference:
[1] Podolin PL, Callahan JF, Bolognese BJ, Li YH, Carlson K, Davis TG, Mellor GW, Evans C, Roshak AK. Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3 -thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation. J Pharmacol Exp Ther. 2005 Jan;312(1):373-81.
| Cell experiment [1]: | |
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Cell lines |
Human Monocytes |
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Preparation method |
The solubility of this compound in DMSO is >14mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0.1, 0.3, 1, 3 and 10 μM; 30 min |
|
Applications |
In human peripheral blood monocytes, TPCA-1 inhibited the production of TNF-α, IL-6, and IL-8 induced by LPS in a concentration-dependent way with IC50 values of 170, 290, and 320 nM, respectively. |
| Animal experiment [1]: | |
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Animal models |
collagen-immunized/boosted DBA/1 mice |
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Dosage form |
3, 10, or 20 mg/kg, i.p., b.i.d., from days 1 to 48. |
|
Application |
In collagen-immunized/boosted DBA/1 mice, TPCA-1 (20 or 10 mg/kg) dose-dependently reduced the severity of arthritis, resulting in a significantly decreased mean clinical score and delaying time to onset of disease. TPCA-1 (10 mg/kg, i.p., b.i.d.) also inhibited p65 nuclear localization and paw tissue levels of IL-1β, IL-6, TNF-α, and IFN-γ. |
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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. |
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References: [1] Podolin PL, Callahan JF, Bolognese BJ, Li YH, Carlson K, Davis TG, Mellor GW, Evans C, Roshak AK. Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3 -thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation. J Pharmacol Exp Ther. 2005 Jan;312(1):373-81. | |
| Cas No. | 507475-17-4 | SDF | |
| Chemical Name | 2-(carbamoylamino)-5-(4-fluorophenyl)thiophene-3-carboxamide | ||
| Canonical SMILES | C1=CC(=CC=C1C2=CC(=C(S2)NC(=O)N)C(=O)N)F | ||
| Formula | C12H10FN3O2S | M.Wt | 279.29 |
| Solubility | ≥ 13.95mg/mL in DMSO, ≥ 2.53 mg/mL in EtOH with ultrasonic and warming | Storage | Desiccate 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 | 3.5805 mL | 17.9025 mL | 35.8051 mL |
| 5 mM | 0.7161 mL | 3.5805 mL | 7.161 mL |
| 10 mM | 0.3581 mL | 1.7903 mL | 3.5805 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 30 reference(s) in Google Scholar.)
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