For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>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.<br>IC50 value:17.9 nM<br>Target: IKK-2<br>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.<br>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.</p>
| Catalog Number | I003804 |
| CAS Number | 507475-17-4 |
| Synonyms | 2-(carbamoylamino)-5-(4-fluorophenyl)thiophene-3-carboxamide |
| Molecular Formula | C₁₂H₁₀FN₃O₂S |
| Purity | ≥95% |
| Target | IκB/IKK |
| Solubility | DMSO 56 mg/ml; Water <1 mg/ml |
| Storage | 3 years -20C powder |
| IC50 | 17.9 nM |
| InChI | InChI=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) |
| InChIKey | SAYGKHKXGCPTLX-UHFFFAOYSA-N |
| SMILES | C1=CC(=CC=C1C2=CC(=C(S2)NC(=O)N)C(=O)N)F |
| Reference | </br>1:Breaking resistance of pancreatic cancer cells to an attenuated vesicular stomatitis virus through a novel activity of IKK inhibitor TPCA-1. Cataldi M, Shah NR, Felt SA, Grdzelishvili VZ.Virology. 2015 Nov;485:340-54. doi: 10.1016/j.virol.2015.08.003. Epub 2015 Aug 29. PMID: 26331681 Free PMC Article</br>2:IKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced choroidal neovascularization and macrophage recruitment. Gaddipati S, Lu Q, Kasetti RB, Miller MC, Lu Q, Trent JO, Kaplan HJ, Li Q.PLoS One. 2015 Mar 24;10(3):e0121185. doi: 10.1371/journal.pone.0121185. eCollection 2015. PMID: 25803615 Free PMC Article</br>3:TPCA-1 is a direct dual inhibitor of STAT3 and NF-κB and regresses mutant EGFR-associated human non-small cell lung cancers. Nan J, Du Y, Chen X, Bai Q, Wang Y, Zhang X, Zhu N, Zhang J, Hou J, Wang Q, Yang J.Mol Cancer Ther. 2014 Mar;13(3):617-29. doi: 10.1158/1535-7163.MCT-13-0464. Epub 2014 Jan 8. PMID: 24401319 Free Article</br>4:Inhibition of type I interferon-mediated antiviral action in human glioma cells by the IKK inhibitors BMS-345541 and TPCA-1. Du Z, Whitt MA, Baumann J, Garner JM, Morton CL, Davidoff AM, Pfeffer LM.J Interferon Cytokine Res. 2012 Aug;32(8):368-77. doi: 10.1089/jir.2012.0002. Epub 2012 Apr 17. PMID: 22509977 Free PMC Article</br>5:IKK-2 inhibitor TPCA-1 represses nasal epithelial inflammation in vitro. Sachse F, Becker K, Basel TJ, Weiss D, Rudack C.Rhinology. 2011 Jun;49(2):168-73. doi: 10.4193/Rhino10.099. PMID: 21743871 </br>6: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. Podolin PL, Callahan JF, Bolognese BJ, Li YH, Carlson K, Davis TG, Mellor GW, Evans C, Roshak AK.J Pharmacol Exp Ther. 2005 Jan;312(1):373-81. Epub 2004 Aug 17. PMID: 15316093 Free Article |
