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| Product Name: | TPCA-1 | | Synonyms: | TPCA-1;2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide;5-(4-Fluorophenyl)-2-ureidothiophene-3-carboxamide;TPCA-1(TPCA 1);3-ThiophenecarboxaMide, 2-[(aMinocarbonyl)aMino]-5-(4-fluorophenyl)-;5-(4-Fluorophenyl)-2-ureidothiophene-3-carboxamide TPCA-1;TPCA-1
IKK-2 Inhibitor IV;GW683965 | | CAS: | 507475-17-4 | | MF: | C12H10FN3O2S | | MW: | 279.29 | | EINECS: | | | Product Categories: | NF-kB | | Mol File: | 507475-17-4.mol |  |
| | TPCA-1 Chemical Properties |
| Melting point | >217°C (dec.) | | Boiling point | 442.6±45.0 °C(Predicted) | | density | 1.490 | | storage temp. | 2-8°C | | solubility | DMSO: soluble5mg/mL, clear | | form | powder | | pka | 13.12±0.50(Predicted) | | color | white to light brown | | Stability: | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Codes | Xn | | Risk Statements | 22-36 | | Safety Statements | 26 | | WGK Germany | 3 |
| | TPCA-1 Usage And Synthesis |
| Description | TPCA-1 (507475-17-4) selective inhibitor of IκB kinase 2 (IKK2) (IC50 = 17.9 nM).1 Inhibits production of pro-inflammatory cytokines in arthritis and other animal models of inflammation.1,2 Also attenuates NLRP3 inflammasome activation in THP-1 myeloid cells, and suppresses IL1β-induced proliferation, migration, and invasion of HeLa cells.3,4 Continuous exposure to TPCA-1 promotes expansion of hematopoietic stem/progenitor cells (HSPCs) via improved glycolysis and limited ROS production.5 | | Uses | TPCA-1 is a direct dual inhibitor for both IKKβ (IKK-2) and STAT3. It inhibits STAT3 phosphorylation, DNA binding, and transactivation in vivo. Synergistic treatment of TPCA-1 with tyrosine kinase inhibitors (TKIs) can potentially be a more effective method for treating cancers. | | Definition | ChEBI: 2-(carbamoylamino)-5-(4-fluorophenyl)-3-thiophenecarboxamide is a member of thiophenes and an aromatic amide. | | Biological Activity | Potent, selective inhibitor of I κ B kinase-2 (IKK-2) (IC 50 = 17.9 nM) that displays > 22-fold selectivity over IKK-1 and > 550-fold selectivity over other kinases and enzymes. Inhibits production of pro-inflammatory cytokines in vitro and in vivo and inhibits NF- κ B nuclear localisation. Reduces the severity and onset of collagen-induced arthritis; anti-inflammatory. | | Biochem/physiol Actions | TPCA-1 is a potent and selective inhibitor of human IκB kinase-2 (IKK-2) with IC50 = 17.9 nM for IKK-2 compared to 400nm for IKK-1. It has been used to study inhibition of IKK-2 to prevent inflammatory mediator release in animal models of arthritis and airway inflammation. | | 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]. | | storage | Store at -20°C | | References | Podolin et al. (2005), Attenuation of murine collagen-induced arthritis by a novel, 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; Pharmacol. Exp. Ther., 312 373
Wang et al. (2021), TPCA-1 negatively regulates inflammation mediated by NF-kB pathway in mouse chronic periodontitis model; Oral Microbiol., 36 192
Unterreiner et al. (2021), Pharmacological inhibition of IKKb dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1; Biophys. Res. Commun., 545 177
Tao et al. (2021), IL-1b promotes cervical cancer though activating NF-κB/CCL-2; J. Exp. Pathol., 14 426
Sun et al. (2021), Continuous NF-κB pathway inhibition promotes expansion of human phenotypical hematopoietic stem/progenitor cells through metabolism regulation; Cell Res., 399 112468 |
| | TPCA-1 Preparation Products And Raw materials |
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