S1697

SPD304

≥98% (HPLC), solid

• Synonym(s): 6,7-Dimethyl-3-[[methyl[2-[methyl[[1-[3-(trifluoromethyl)phenyl]-1H-indol-3-yl]methyl]amino]ethyl]amino]methyl]-(4H-1-Benzopyran-4-one dihydrochloride, SPD00000304
• Empirical Formula (Hill Notation): C₃₂H₃₂F₃N₃O₂ · 2HCl
• CAS Number: 1049741-03-8
• Molecular Weight: 620.53
• MDL number: MFCD09265259
• UNSPSC Code: 51111800
• PubChem Substance ID: 24724602
• NACRES: NA.77

Properties

• Quality Level: 100
• assay: ≥98% (HPLC)
• form: solid
• color: white
• solubility: H₂O: >5 mg/mL
• storage temp.: 2-8°C
• SMILES string: Cl.Cl.CN(CCN(C)Cc1cn(-c2cccc(c2)C(F)(F)F)c3ccccc13)CC4=COc5cc(C)c(C)cc5C4=O
• InChI: 1S/C32H32F3N3O2.2ClH/c1-21-14-28-30(15-22(21)2)40-20-24(31(28)39)18-37(4)13-12-36(3)17-23-19-38(29-11-6-5-10-27(23)29)26-9-7-8-25(16-26)32(33,34)35;;/h5-11,14-16,19-20H,12-13,17-18H2,1-4H3;2*1H
• InChI key: GOZMBJCYMQQACI-UHFFFAOYSA-N
• Gene Information: human ... TNF(7124) ; mouse ... TNF(21926) ; rat ... TNF(24835)

Description

Application

SPD304 has been used in the inhibition of tumor necrosis factor receptor 1 (TNFR1) in dorsal root ganglion neurons and tumor necrosis factor alpha in colonic epithelial cell lines.

SPD304 may be used in TNF-α-mediated cell signaling studies.

Biochem/physiol Actions

SPD304 is a small molecule inhibitor of TNF-a activity with a novel mechanism of action. It interferes with protein-protein interactions on the contact surfaces of the trimeric TNF-a subunits, displacing one of the trimer units, resulting in dissociation of the trimer and loss of activity at the receptor TNFR1. SPD304 inhibits TNFR1 receptor binding to TNF-a with an IC₅₀ of 22μM in vitro and inhibits TNF-a-mediated stimulation of IkB degradation in HeLa cells with an IC₅₀ of 4.6 μM.

Trimerization of TNF-α is essential for its biological activity. SPD304 inhibits the trimerization by interacting with Glycine 122 residue. It also inhibits the activity of Receptor activator of nuclear factor-κB ligand (RANKL) by similar interaction.

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• ppe: dust mask type N95 (US), Eyeshields, Gloves