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T-5224

Catalog No.GC16165

T-5224 Chemical Structure

C-Fos/AP-1 inhibitor

Size Price Stock Qty
10mM (in 1mL DMSO)
$83.00
In stock
5mg
$73.00
In stock
10mg
$115.00
In stock
50mg
$343.00
In stock
100mg
$577.00
In stock
500mg
$1,236.00
In stock

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Sample solution is provided at 25 µL, 10mM.

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Quality Control & SDS

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Protocol

Kinase experiment [1]:

Inhibitory activities

The DNA binding activity of transcription factors was measured using the TransAM kits (Active Motif). Nuclear extracts containing factors such as c-Fos/AP-1, c-Jun/AP-1, ATF-2, C/EBPa, MyoD, Sp-1 or NF-kB/p65 and various concentrations of T-5224 were added in the multi-well plates precoated with respective consensus double-stranded (ds)DNA oligomers. After incubation for 1 h, the transcription factor bound to its respective consensus dsDNA sequences was detected by using antibodies reactive against the respective transcription factors according to the manufacturer’s protocol.

Cell experiment [2]:

Cell lines

Human synovial SW982 cells; human chondrocyte SW1353 cells

Preparation method

Dissolved in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

0.1, 1, 10, 100, 1000 μM.

Applications

In human synovial SW982 cells stimulated by IL-1β, T-5224 inhibits the production of MMP-1, MMP-3, IL-6 and TNFα. In human chondrocyte SW1353 cells stimulated by IL-1β, T-5224 inhibits the production of MMP-3 and MMP-13 with IC50 value of 10 μM.

Animal experiment [3]:

Animal models

Male DBA/1J mice with type II collagen–induced arthritis (CIA).

Dosage form

0.3, 1, 3, 30 mg/kg, once daily from day 21, before the onset of arthritis; administered orally.

Applications

T-5224 significantly inhibits the development of arthritis by 64% and 91% on day 50 at 3 and 30 mg/kg, respectively. T-5224 inhibits joint destruction and completely protects the joint from destruction at 30 mg/kg. At 30 mg/kg dose, T-5224 significantly inhibits MMP-2, MMP-3, MMP-9, MMP-13, IL-1β, IL-6 and TNFα.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Aikawa Y, Morimoto K, Yamamoto T, et al. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol, 2008, 26(7): 817-823.

Background

T-5224 is a non-peptidic, small molecule and novel inhibitor of c-Fos/AP-1 [1].

T-5224 has shown the specific inhibition in a c-Fos/AP-1promoter-luciferase assay, without affecting the levels of c-Fos family protein members themselves. In addition, T-5224 has been reported to selectively inhibit the DNA binding activity of c-Fos/c-Jun, without affecting those of other transcription factors(C/EBPα and ATF-2, MyoD, Sp-1 and NF-κB/p65). Some research has been suggested that T-5224 potently suppressed the development of collagen-induced arthritis (CIA). Besides, T-5224 has been evidenced to inhibit the expression of nuclear factor of activated T-cells (NFAT) and osteoclastogenesis of the macrophage-osteoclast precursor RAW264.7cells induced by receptor activator of NF-κB ligand (RANKL). Apart from these, T-5224 has been noted to inhibit in-vitro production of the mediators (MMP-1, MMP-3, IL-6 and TNF-α) in IL-1β-stimulated human synovial SW982 cells with the mean IC50 of about 10μM. In the in vivo pharmacokinetic analysis, the ED50 of T-5224 is about 1-10mg/kg, and the Cmax is 0.03-0.5μM [1].

References:
[1] Aikawa Y1, Morimoto K, Yamamoto T, Chaki H, Hashiramoto A, Narita H, Hirono S, Shiozawa S. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat Biotechnol. 2008 Jul;26(7):817-23.

Chemical Properties

Cas No. 530141-72-1 SDF
Synonyms N/A
Chemical Name 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-oxo-2,3-dihydrobenzo[d]isoxazol-6-yl)methoxy)phenyl)propanoic acid
Canonical SMILES O=C1NOC2=CC(COC(C=CC(C(C3=C(O)C=C(OC4CCCC4)C=C3)=O)=C5)=C5CCC(O)=O)=CC=C12
Formula C29H27NO8 M.Wt 517.53
Solubility ≥ 25.88mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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