TPCA-1 - CAS 507475-17-4

TPCA-1 is potent, selective inhibitor of IKK-2 (IC50 = 17.9 nM) that displays > 22-fold selectivity over IKK-1 and > 550-fold selectivity over other kinases and enzymes.
IC50 value:17.9 nM
Target: IKK-2
in vitro: In a time-resolved fluorescence resonance energy transfer assay, TPCA-1 inhibits human IKK-2 activity with an IC50 of 17.9 nM. In addition, TPCA-1 is demonstrated to be ATP-competitive. Besides, TPCA-1 exhibits IC50 values of 400 nM and 3600 nM against IKK-1 and JNK3, respectively. TPCA-1 inhibits the production of TNF-α, IL-6, and IL-8 in a concentration-dependent manner, exhibiting IC50 values of 170, 290, and 320 nM, respectively. TPCA-1 inhibits glioma cell proliferation, as well as TNF-induced RelA (p65) nuclear translocation and NFκB-dependent IL8 gene expression. Importantly, TPCA-1 inhibits IFN-induced gene expression, completely suppressing MX1 and GBP1 gene expression, while having only a minor effect on ISG15 expression.
in vivo: Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg, i.p., b.i.d., results in a dose-dependent reduction in the severity of murine collagen-induced arthritis (CIA). The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg, i.p., b.i.d. are comparable to the effects of the antirheumatic drug, etanercept, when administered prophylactically at 4 mg/kg, i.p., every other day. Nuclear localization of p65, as well as levels of IL-1beta, IL-6, TNF-alpha, and interferon-gamma, is significantly reduced in the paw tissue of TPCA-1- and etanercept-treated mice. In addition, administration of TPCA-1 in vivo results in significantly decreased collagen-induced T cell proliferation ex vivo. Therapeutic administration of TPCA-1 at 20 mg/kg, but not at 3 or 10 mg/kg, i.p., b.i.d., significantly reduces the severity of CIA, as does etanercept administration at 12.5 mg/kg, i.p., every other day.

Catalog Number: I003804

CAS Number: 507475-17-4

PubChem Substance ID:355040796

Molecular Formula: C₁₂H₁₀FN₃O₂S

Molecular Weight:279.29

Purity: ≥95%

* For research use only. Not for human or veterinary use.

Synonym

Synonyms2-(carbamoylamino)-5-(4-fluorophenyl)thiophene-3-carboxamide

Property

Molecular Formula: C₁₂H₁₀FN₃O₂S
Molecular Weight279.29
Target:IκB/IKK
SolubilityDMSO 56 mg/ml; Water <1 mg/ml
Purity≥95%
Storage3 years -20C powder
MDLMFCD09037541
IC5017.9 nM

Computed Descriptor

InChIInChI=1S/C12H10FN3O2S/c13-7-3-1-6(2-4-7)9-5-8(10(14)17)11(19-9)16-12(15)18/h1-5H,(H2,14,17)(H3,15,16,18)
InChIKeySAYGKHKXGCPTLX-UHFFFAOYSA-N
SMILESC1=CC(=CC=C1C2=CC(=C(S2)NC(=O)N)C(=O)N)F