| Identification | Back Directory | [Name]
Benzenepropanoic acid, 5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(2,3-dihydro-3-oxo-1,2-benzisoxazol-6-yl)Methoxy]- | [CAS]
530141-72-1 | [Synonyms]
T-5224
T-5225
CS-1217
TP-5224
T-5224; T5224; T 5224.
3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-oxo-2,3-dihydrobenzo[d]isoxazol-6-yl)methoxy)
3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo-[d]isoxazol-6-yl)methoxy)phenyl)
3-[5-[4-(cyclopentoxy)-2-hydroxy-benzoyl]-2-[(3-hydroxy-1,2-benzo xazol-6-yl)methoxy]phenyl]propanoic acid
Benzenepropanoic acid, 5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(2,3-dihydro-3-oxo-1,2-benzisoxazol-6-yl)Methoxy]- | [Molecular Formula]
C29H27NO8 | [MDL Number]
MFCD28053483 | [MOL File]
530141-72-1.mol | [Molecular Weight]
517.53 |
| Chemical Properties | Back Directory | [density ]
1.376±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:30.5(Max Conc. mg/mL);58.93(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:2):0.33(Max Conc. mg/mL);0.64(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);57.97(Max Conc. mM) | [form ]
A crystalline solid | [pka]
4.61±0.10(Predicted) | [color ]
White to yellow | [InChIKey]
DALCQQSLNPLQFZ-UHFFFAOYSA-N | [SMILES]
C1(CCC(O)=O)=CC(C(=O)C2=CC=C(OC3CCCC3)C=C2O)=CC=C1OCC1=CC2=C(C=C1)C(=O)NO2 |
| Hazard Information | Back Directory | [Description]
T-5224 is an inhibitor of c-fos/activator protein 1 (AP-1). It inhibits the DNA binding activity of c-fos/AP-1 without affecting the activity of C/EBPα, ATF2, MyoD, Sp1, and NF-κB/p65 in vitro.1 It shows inhibitory activity in a c-fos/AP-1 promoter luciferase assay without changing c-fos family protein expression levels in TNF-α-stimulated NIH/3T3 cells. Administration of T-5224 (30 mg/kg) inhibits the development of collagen-induced arthritis in mice through reduction of IL-1β production, neutrophil infiltration, and synovial cell proliferation.2 It reduces the inflammatory cytokine response in LPS-challenged mice, lowering levels of TNF-α and HMGB1 in the serum and MIP-1α and MCP-1 in the liver. T-5224 reduces in vivo necrosis of liver tissue and improves survival rates in LPS-challenged mice. T-5224 also exhibits anticancer activity, reducing proliferation and migration of HSC-3-M3 head and neck squamous carcinoma cells in vitro and the number of metastases in an HSC-3-M3 orthotopic xenograft model in vivo.3 | [Uses]
T-5224 is a selective activator protein-1 inhibitor that prevents lymph node metastasis in an oral cancer model. | [in vivo]
Administration of T-5224 (300 mg/kg, p.o.) after intraperitoneal injection of LPS impartes appreciable protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1, and reduces the lethality (27%)[4].
G2 is observed in rat and monkey liver microsomes as a major metabolite of T-5224, suggesting that G2 is not a human-specific metabolite[5].
T-5224 (300 mg/kg, p.o.) inhibits the production of TNF-alpha and other downstream effectors in C57BL/6 mice[6]. | [IC 50]
c-Fos | [storage]
Store at -20°C | [References]
[1] YUKIHIKO AIKAWA. Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1[J]. Nature biotechnology, 2008, 26 7: 817-823. DOI: 10.1038/nbt1412
[2] SHINICHIRO IZUTA. T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice.[J]. Biotechnology Letters, 2012, 34 12: 2175-2182. DOI: 10.1007/s10529-012-1022-4
[3] DAISUKE KAMIDE. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model[J]. Cancer Science, 2016, 107 5: 666-673. DOI: 10.1111/cas.12914 |
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