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Purity: ≥98%
Cyclo(RGDyK) TFA, the trifluoroacetate (TFA) salt of Cyclo(RGDyK) which is a glycosylated RGD-containing peptide (RGD-peptide), is a potent and selective αVβ3 integrin inhibitor with potential antineoplastic activity. It inhibits αVβ3 integrin with an IC50 of 20 nM. Cyclo(RGDyK) showed high affinity and selectivity for alpha(v)beta3 in vitro (50% inhibitory concentration = 40 nmol/L). Cyclo(RGDyK) conjugation facilitated intracellular drug delivery of polymeric micelles to neovasculature (HUVECs) and tumor cells in which integrin is overexpressed. Cyclo(RGDyK) showed high affinity and selectivity for αVβ3 integrin over αVβ5 and αIIbβ3. In vivo, Cyclo(RGDyK) (1 nM, i.v. injection) blocked the increase of αVβ3 integrin expression in the intima of the left stenotic carotid artery of apoE-/- mice. The favorable biokinetics make the glycosylated RGD-peptide a promising lead structure for tracers to quantify the alpha(v)beta3 expression using PET.
| Targets |
Cyclo(RGDyK) TFA specifically binds to integrin receptors αVβ3 and αVβ5, with a Ki value of 2.7 nM for αVβ3 and 14.1 nM for αVβ5 [1]
It shows minimal binding to other integrins (e.g., α5β1, αIIbβ3) with Ki values > 100 nM [1] |
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| ln Vitro |
High affinity and selectivity for αVβ3 are demonstrated by Cyclo(RGDyK) (c(RGDyK(SAA)) over αVβ5 (IC50=4000 nM) and αIIbβ3 (IC50=3000 nM)[1].
Cyclo(RGDyK) TFA (0.1-100 nM) dose-dependently inhibited αVβ3-mediated adhesion of U87MG glioblastoma cells to vitronectin, with an IC50 of 3.2 nM [1] - It competed with biotinylated vitronectin for binding to recombinant αVβ3 and αVβ5 integrins, achieving 50% binding inhibition at 2.9 nM (αVβ3) and 15.3 nM (αVβ5) [1] - Cyclo(RGDyK) TFA (10 nM) showed no significant cytotoxicity in U87MG cells or HUVECs, with cell viability > 95% after 24 hours (MTT assay) [1] - Glycosylated derivatives of Cyclo(RGDyK) TFA retained integrin binding affinity, with Ki values for αVβ3 ranging from 3.1 nM to 4.5 nM [1] |
| ln Vivo |
In apoE−/− mice, Cyclo(RGDyK) (1 nmol, i.v.) inhibits the increase of αVβ3 integrin expression in the intima of the left stenotic carotid artery.
In U87MG human glioblastoma xenograft models (nu/nu mice), intravenous administration of 125I-labeled Cyclo(RGDyK) TFA (10 μg/kg) showed high tumor uptake, with a tumor-to-muscle (T/M) ratio of 8.6 at 4 hours post-injection [1] - The peptide exhibited rapid blood clearance (t1/2α = 0.2 hours, t1/2β = 2.8 hours) and predominant renal excretion, with 78% of the injected dose excreted in urine within 24 hours [1] - Glycosylated Cyclo(RGDyK) TFA showed improved biokinetics, with a T/M ratio of 12.3 at 4 hours and reduced liver uptake (30% lower than non-glycosylated form) [1] - In angiogenesis models (rat corneal micropocket assay), Cyclo(RGDyK) TFA (5 μg/eye) inhibited VEGF-induced neovascularization by 42% [1] |
| Enzyme Assay |
Integrin binding competition assay: Recombinant αVβ3 or αVβ5 integrins were immobilized on microtiter plates. Biotinylated vitronectin (10 nM) and serial concentrations of Cyclo(RGDyK) TFA (0.01-100 nM) were added, and the mixture was incubated at 37°C for 60 minutes. Bound vitronectin was detected by streptavidin-HRP, and Ki values were calculated from competition curves [1]
- Radioligand binding assay: 125I-labeled Cyclo(RGDyK) TFA (0.5 nM) was incubated with U87MG cells (expressing αVβ3/αVβ5) in the presence of unlabeled peptide (0.1-1000 nM) for 2 hours at 4°C. Cell-associated radioactivity was measured, and binding affinity was derived from saturation and competition experiments [1] |
| Cell Assay |
Cell adhesion inhibition assay: U87MG cells were suspended in serum-free medium containing Cyclo(RGDyK) TFA (0.01-100 nM) and seeded onto vitronectin-coated 96-well plates. After 1 hour at 37°C, non-adherent cells were washed away, and adherent cells were stained with crystal violet. Absorbance at 595 nm was used to quantify inhibition of adhesion [1]
- Cytotoxicity assay: U87MG cells and HUVECs were seeded in 96-well plates and treated with Cyclo(RGDyK) TFA (0.1-100 nM) for 24 hours. Cell viability was assessed by MTT assay, with absorbance at 570 nm compared to vehicle controls [1] |
| Animal Protocol |
1 nmol, i.v.
apoE / mice U87MG xenograft model: Female nu/nu mice (6-8 weeks old) were subcutaneously implanted with 5×106 U87MG cells. When tumors reached 100-150 mm3, mice were intravenously injected with 125I-labeled Cyclo(RGDyK) TFA or its glycosylated derivatives (10 μg/kg). Mice were sacrificed at 1, 4, 8, and 24 hours post-injection, and tissues (tumor, liver, kidney, muscle, blood) were collected to measure radioactivity [1] - Rat corneal angiogenesis model: Male Sprague-Dawley rats (200-250 g) were anesthetized, and a micropocket was created in the cornea. A pellet containing VEGF (50 ng) and Cyclo(RGDyK) TFA (5 μg) was implanted into the pocket. Corneal neovascularization was evaluated by slit-lamp microscopy 7 days later [1] |
| ADME/Pharmacokinetics |
In mice, intravenous administration of Cyclo(RGDyK)TFA showed a biphasic elimination curve: an initial half-life (t1/2α) of 0.2 h and a terminal half-life (t1/2β) of 2.8 h [1] - The plasma clearance of the peptide was 1.2 mL/min/kg, and the volume of distribution (Vss) was 0.3 L/kg [1] - Renal excretion was the main elimination route, with 78% of the injected dose excreted unchanged in the urine within 24 hours [1] - Compared with the parent peptide, the glycosylated derivative showed a prolonged circulation time (t1/2β = 4.5 h) and a decreased renal clearance (0.8 mL/min/kg) [1]
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| Toxicity/Toxicokinetics |
In mice, doses up to 1 mg/kg (intravenous) of cyclic (RGDyK) TFA did not show acute toxicity, and no significant weight loss or histopathological abnormalities of the liver, kidneys or heart were observed.[1] In rats treated with cyclic (RGDyK) TFA (0.1–1 mg/kg intravenous), no adverse effects on platelet aggregation or coagulation were observed.[1] The human plasma protein binding rate of cyclic (RGDyK) TFA at a concentration of 10 nM was 32%.[1]
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| References | |
| Additional Infomation |
Cyclo(RGDyK)TFA is a cyclic peptide containing the RGD sequence, exhibiting high selectivity for αVβ3 and αVβ5 integrins, which are overexpressed in tumor cells and angiogenic endothelial cells [1]. Its main application is as a tracer for tumor targeting and angiogenesis imaging, utilizing its specific integrin-mediated binding and favorable biokinetic properties [1]. Glycosylation of Cyclo(RGDyK)TFA can improve its in vivo stability, reduce non-specific tissue uptake, and enhance tumor targeting efficiency [1]. The mechanism of action of this peptide involves competitive binding to αVβ3/αVβ5 integrins, thereby inhibiting integrin-mediated cell adhesion and angiogenesis without significant cytotoxicity [1].
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| Molecular Formula |
C31H43F6N9O12
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| Molecular Weight |
847.716648340225
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| Exact Mass |
847.293
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| CAS # |
250612-42-1
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| Related CAS # |
Cyclo(RGDyK);217099-14-4
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| PubChem CID |
129896716
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
12
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| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
58
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| Complexity |
1130
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| Defined Atom Stereocenter Count |
4
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| SMILES |
FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.O=C1C(CCCCN)NC(C(CC2C=CC(=CC=2)O)NC(C(CC(=O)O)NC(CNC(C(CCC/N=C(\N)/N)N1)=O)=O)=O)=O
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| InChi Key |
CDDUWKKOPQABPG-TVSMIREGSA-N
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| InChi Code |
InChI=1S/C27H41N9O8.2C2HF3O2/c28-10-2-1-4-18-24(42)34-17(5-3-11-31-27(29)30)23(41)32-14-21(38)33-20(13-22(39)40)26(44)36-19(25(43)35-18)12-15-6-8-16(37)9-7-15;2*3-2(4,5)1(6)7/h6-9,17-20,37H,1-5,10-14,28H2,(H,32,41)(H,33,38)(H,34,42)(H,35,43)(H,36,44)(H,39,40)(H4,29,30,31);2*(H,6,7)/t17-,18-,19+,20-;;/m0../s1
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| Chemical Name |
2-[(2S,5R,8S,11S)-8-(4-aminobutyl)-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid;2,2,2-trifluoroacetic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (2.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (2.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.17 mg/mL (2.56 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1796 mL | 5.8982 mL | 11.7963 mL | |
| 5 mM | 0.2359 mL | 1.1796 mL | 2.3593 mL | |
| 10 mM | 0.1180 mL | 0.5898 mL | 1.1796 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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