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.

Physicochemical Properties

Molecular Formula	C₂₇H₄₁N₉O₇
Molecular Weight	603.67
Exact Mass	603.312
CAS #	161552-03-0
Related CAS #	Cyclo(-RGDfK) TFA;500577-51-5
PubChem CID	10196873
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Index of Refraction	1.666
LogP	-3.1
Hydrogen Bond Donor Count	9
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	12
Heavy Atom Count	43
Complexity	1010
Defined Atom Stereocenter Count	4
SMILES	C1C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CCCN=C(N)N)CCCCN)CC2=CC=CC=C2)CC(=O)O
InChi Key	NVHPXYIRNJFKTE-HAGHYFMRSA-N
InChi Code	InChI=1S/C27H41N9O7/c28-11-5-4-9-18-24(41)34-17(10-6-12-31-27(29)30)23(40)32-15-21(37)33-20(14-22(38)39)26(43)36-19(25(42)35-18)13-16-7-2-1-3-8-16/h1-3,7-8,17-20H,4-6,9-15,28H2,(H,32,40)(H,33,37)(H,34,41)(H,35,42)(H,36,43)(H,38,39)(H4,29,30,31)/t17-,18-,19+,20-/m0/s1
Chemical Name	2-[(2S,5R,8S,11S)-8-(4-aminobutyl)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
Synonyms	Cyclo (-RGDfK)
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	Cyclo(-RGDfK), which has an IC50 of 0.94 nM, is a strong and specific αvβ3 integrin inhibitor[1]. [66 Gal]DOTA-E–[c(RGDfK)]2, with moderate protein binding, in vitro stability, high radiochemical purity (>97%), and specific activity (36-67GBq/μM), can be prepared. Contrasting tumors reflecting αvβ3-targeted tracer accumulation were seen in microPET imaging up to 24 hours after injection[2].
ln 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.
Animal Protocol	N/A Mice
References	[1]. Benefits of NOPO as chelator in gallium-68 peptides, exemplified by preclinical characterization of (68)Ga-NOPO-c(RGDfK). Mol Pharm. 2014 May 5;11(5):1687-95. [2]. Preparation and preclinical evaluation of (66)Ga-DOTA-E(c(RGDfK))2 as a potential theranostic radiopharmaceutical. Nucl Med Biol. 2015 Feb;42(2):109-14.

Solubility Data

Solubility (In Vitro)

DMSO: 90 mg/mL (199.4 mM) Water:<1 mg/mL Ethanol:16 mg/mL (35.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.45 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 20.8 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: ≥ 2.08 mg/mL (3.45 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.45 mM) (saturation unknown) 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 20.8 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	1.6565 mL	8.2827 mL	16.5653 mL
	5 mM	0.3313 mL	1.6565 mL	3.3131 mL
	10 mM	0.1657 mL	0.8283 mL	1.6565 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.