Cyclo(-RGDfK) is a potent, selective and cyclo-peptide-based αvβ3 integrin inhibitor with potential antitumor activity. The constant of affinity (KD) of Cyclo (-RGDfK-) for purified integrin is 41.70 nM. Cyclo (-RGDfK) can react with HEK293(β3) cells moderately. Cyclo(-RGDfK-) modified micelles shows strong affinity to T-24 cells and strong inhibitory effect on the proliferation of T-24 cells.
理化性质和储存条件
| Molecular Weight (MW) | 603.67 |
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| Formula | C27H41N9O7 |
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| CAS No. | 161552-03-0 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 90 mg/mL (199.4 mM) |
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| Water: <1 mg/mL |
| Ethanol: 16 mg/mL (35.4 mM) |
| Synonyms | Cyclo (-RGDfK) |
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| SMILES | O=C([C@H](CCCCN)NC([C@@H](CC1=CC=CC=C1)NC([C@H](CC(O)=O)NC(CN2)=O)=O)=O)N[C@@H](CCCNC(N)=N)C2=O
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实验参考方法
| In Vitro | In vitro activity: The constant of affinity (KD) of Cyclo (-RGDfK-) for purified integrin is 41.70 NM. Cyclo (-RGDfK) is reacting with HEK293(β3) cells moderately. Cyclo(-RGDfK-) modified micelles shows strong affinity to T-24 cells and strong inhibitory effect on the proliferation of T-24 cells.
Kinase Assay: Purified integrin (1 μg/mL; 4℃) is used to coat 96-well microtitre plates, which are then blocked with bovine serum albumin (BSA) (3% in 1 mM CaCl2, 1 mM MgCl2,10 pM MnCl2, 100 mM NaC1,50 mM trishydroxymethyl-aminomethane; pH 7.4), and incubated (3 h at 30 ℃) with biotinylated ligands (1 pg/mL in binding buffer: 0.1% BSA, 1 mM CaCl2,1 mM MgCl2, 10 μM MnCl2, 100 mM NaCl, 50 mM trishydroxymethyl-aminomethane; pH 7.4) in the presence or absence of serially diluted peptides. After washing (3×5 min with binding buffer), bound biotinylated ligand is detected with alkaline-phosphatase conjugated goat antibiotin antibodies (1 μg/mL; 1 h, 37℃), using p-nitrophenyl phosphate as chromogen. Cyclo (-RGDfK) binding in the absence of competitor is defined as 100% signal; binding to blocked wells in the absence of integrin is defined as 0%. Concentrations of Cyclo (-RGDfK) required for 50% inhibition of signal (IC50 values) are estimated graphically.
Cell Assay: In one study where this peptide was labeled with 125I, it was found to bind specifically and with high affinity to αvβ3 receptors on neovascular blood vessel sections of different major human cancers. The integrin alpha(IIb)beta(3)-specific cyclic hexapeptide contains an Arg-Gly-Asp (RGD) sequence. |
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| In Vivo | In athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas, Cyclo (-RGDfK-) modification induces less tumor progression, less tumor metabolic activity, fewer intratumoral vessels. |
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| Animal model | Mice |
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| Formulation & Dosage | N/A |
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| References | Mol Ther. 2009 May;17(5):837-43; J Biomed Nanotechnol. 2014 Mar;10(3):393-404. |
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