Home NF-κB IκB/IKK inhibitor - NF-κB inhibitor - STAT inhibitor - Apoptosis related activator TPCA-1 For research use only.

TPCA-1

Synonyms: GW683965

TPCA-1 (GW683965) is an inhibitor of IKK-2 with IC50 of 17.9 nM in a cell-free assay, inhibits NF-κB pathway, exhibits 22-fold selectivity over IKK-1. TPCA-1 is also an inhibitor of STAT3 and enhances apoptosis.

TPCA-1 Chemical Structure

TPCA-1 Chemical Structure

CAS No. 507475-17-4

Purity & Quality Control

TPCA-1 Related Products

Signaling Pathway

IκB/IKK Signaling Pathways

IκB/IKK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
C57BL/6 mouse BMDM cells Cytotoxicity assay 24 h Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs 22533790
C57BL/6 mouse BMDM cells Function assay 0.5 μM 1 h Antiinflammatory activity in C57BL/6 mouse BMDM cells assessed as inhibition of LPS-stimulated TNFalpha production at 0.5 uM pretreated for 1 hr before LPS challenge after 8 to 24 hrs by immunoassay 22533790
MDA-MB-231 Cytotoxicity assay 3 days Cytotoxicity against human MDA-MB-231 cells assessed as cell growth inhibition after 3 days by presto blue dye based plate reader method 27077228
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description TPCA-1 (GW683965) is an inhibitor of IKK-2 with IC50 of 17.9 nM in a cell-free assay, inhibits NF-κB pathway, exhibits 22-fold selectivity over IKK-1. TPCA-1 is also an inhibitor of STAT3 and enhances apoptosis.
Targets
NF-κB [3] STAT3 [3] IKK2 [1]
(Cell-free assay)
17.9 nM
In vitro
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. [1] 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. [2]
Kinase Assay IKK-2 Assay
Recombinant human IKK-2 (residues 1-756) is expressed in baculovirus as an N-terminal GST-tagged fusion protein, and its activity is assessed using a time-resolved fluorescence resonance energy transfer assay. In brief, IKK-2 (5 nM final) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM CHAPS, pH 7.4, with 1 mM DTT and 0.01% w/v BSA) is added to wells containing various concentrations of compound or DMSO vehicle (3% final). The reaction is initiated by the addition of GST-IκBα substrate (25 nM final)/ATP (1 μM final), in a total volume of 30 μL. The reaction is incubated for 30 min at room temperature, then terminated by the addition of 15 μL of 50 mM EDTA. Detection reagent (15 μL) in buffer (100 mM HEPES, pH 7.4, 150 mM NaCl, and 0.1% w/v BSA) containing antiphosphoserine- IκBα-32/36 monoclonal antibody 12C2, labeled with W-1024 europium chelate, and an allophycocyanin-labeled anti-GST antibody is added, and the reaction is further incubated for 60 min at room temperature. The degree of phosphorylation of GST- IκBαis measured as a ratio of specific 665-nm energy transfer signal to reference europium 620-nm signal, using a Packard Discovery plate reader.
Cell Research Cell lines U87, MT330, SJ-G2, and GBM6 human glioma lines
Concentrations 0-50 μM
Incubation Time 3 days
Method

Ten microliters of MTT from stock solution (10 mg/mL) is added to each well of 96-well plates containing glioma cells and incubated at 37 °C for 2–4 h. Oxidized MTT is solubilized by adding 100 μL of 10% sodium dodecyl sulfate (SDS) in 0.01 N HCL, and plates are incubated at 37 °C for 4 h in a humidified chamber. Plates are read at 570 nm on a plate reader.
In Vivo
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, 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-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. [1]
Animal Research Animal Models Murine collagen-induced arthritis
Dosages 3, 10, or 20 mg/kg
Administration Administered via i.p. or b.i.d.

Chemical Information & Solubility

Molecular Weight 279.29 Formula

C12H10FN3O2S 
CAS No. 507475-17-4 SDF Download TPCA-1 SDF
Smiles C1=CC(=CC=C1C2=CC(=C(S2)NC(=O)N)C(=O)N)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 56 mg/mL ( (200.5 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

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Handling Instructions

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