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.
Product Overview
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.
Storage
Desiccate at-20°C
Molecular Formula
C12H10FN3O2S
Chemical Name
2-(carbamoylamino)-5-(4-fluorophenyl)thiophene-3-carboxamide
Solubility
Soluble in DMSO > 10 mM
Shipping Conditions
Evaluation sample solution: ship with blue ice. All other available size: ship with RT, or blue ice upon request
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.
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.
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