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.

Physicochemical Properties

Molecular Formula	C31H43F6N9O12
Molecular Weight	847.716648340225
Exact Mass	847.293
CAS #	250612-42-1
Related CAS #	Cyclo(RGDyK);217099-14-4
PubChem CID	129896716
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	12
Hydrogen Bond Acceptor Count	20
Rotatable Bond Count	12
Heavy Atom Count	58
Complexity	1130
Defined Atom Stereocenter Count	4
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
InChi Key	CDDUWKKOPQABPG-TVSMIREGSA-N
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
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
Synonyms	Cyclo(RGDyK) trifluoroacetate
HS Tariff Code	2934.99.9001
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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

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].
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.
Animal Protocol	1 nmol, i.v. apoE / mice
References	[1]. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001 Feb;42(2):326-36.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (118.0 mM) Water:100 mg/mL (118.0 mM) Ethanol:20 mg/mL (23.6 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.