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TPCA-1

Catalog No.
A4602
IKK-2 inhibitor,potent and selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$80.00
In stock
5mg
$70.00
In stock
10mg
$120.00
In stock
100mg
$480.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt279.29
Cas No.507475-17-4
FormulaC12H10FN3O2S
Solubility≥13.95mg/mL in DMSO, ≥2.53 mg/mL in EtOH with ultrasonic and warming,insoluble in H2O
Chemical Name2-(carbamoylamino)-5-(4-fluorophenyl)thiophene-3-carboxamide
SDFDownload SDF
Canonical SMILESC1=CC(=CC=C1C2=CC(=C(S2)NC(=O)N)C(=O)N)F
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Cell experiment [1]:

Cell lines

Human Monocytes

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]:

Animal models

collagen-immunized/boosted DBA/1 mice

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.

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] 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.

Biological Activity

Description TPCA-1 is a selective inhibitor of IκB kinase-2 with IC50 values of 17.9 nM and 0.4 μM for IKK-2 and -1, respectively.
Targets IKK-2 IKK-1        
IC50 17.9 nM 0.4 μM        

Quality Control

Chemical structure

TPCA-1

Related Biological Data

TPCA-1

Related Biological Data

TPCA-1

Related Biological Data

TPCA-1

Related Biological Data

TPCA-1