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TPCA-1

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TPCA-1 Basic information

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
Product Categories:
  • NF-kB
Mol File:
507475-17-4.mol
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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.
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Safety Information

Hazard Codes 
Xn
Risk Statements 
22-36
Safety Statements 
26
WGK Germany 
3
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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-1Supplier

3B Pharmachem (Wuhan) International Co.,Ltd.
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821-50328103-801 18930552037
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3bsc@sina.com
Chembest Research Laboratories Limited
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+86-21-20908456
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sales@BioChemBest.com
Jinan Trio PharmaTech Co., Ltd.
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+86 (531) 88811783
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sales@trio-pharmatech.com (International market)
Dalian Meilun Biotech Co., Ltd.
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0411-62910999 13889544652
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sales@meilune.com
Hangzhou Sage Chemical Co., Ltd.
Tel
+86057186818502 13588463833
Email
info@sagechem.com