RGD-4C is an arginine-glycine-aspartate peptide (ACDCRGDCFC) with integrin-binding activity. The Arg-Gly-Asp (RGD) sequence is the major integrin recognition site for extracellular matrix proteins, and peptides containing this sequence can mimic the recognition specificity of matrix proteins. RGD-4C is an αv integrin ligand that can be conjugated to bioactive molecules and exert anti-tumor effects in animal models.

Physicochemical Properties

Molecular Formula	C44H61F3N14O18S4
Molecular Weight	1259.2934
Exact Mass	1258.312
CAS #	332179-76-7
PubChem CID	145707972
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	17
Hydrogen Bond Acceptor Count	27
Rotatable Bond Count	15
Heavy Atom Count	83
Complexity	2260
Defined Atom Stereocenter Count	9
SMILES	S1C([H])([H])[C@@]2([H])C(N([H])[C@]([H])(C(N([H])C([H])([H])C(N([H])[C@@]([H])(C([H])([H])C(=O)O[H])C(N([H])[C@@]([H])(C([H])([H])S1)C(N([H])[C@]([H])(C(N([H])[C@]([H])(C(N([H])C([H])([H])C(=O)O[H])=O)C([H])([H])SSC([H])([H])[C@@]([H])(C(N([H])[C@@]([H])(C([H])([H])C(=O)O[H])C(N2[H])=O)=O)N([H])C([C@]([H])(C([H])([H])[H])N([H])[H])=O)=O)C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)=O)=O)=O)C([H])([H])C([H])([H])C([H])([H])/N=C(\N([H])[H])/N([H])[H])=O.FC(C(=O)O[H])(F)F
InChi Key	WQLVAVHKXVRFPP-AVWCAVILSA-N
InChi Code	InChI=1S/C42H60N14O16S4.C2HF3O2/c1-19(43)33(64)53-26-16-74-73-15-25(35(66)48-14-32(62)63)54-36(67)22(10-20-6-3-2-4-7-20)51-41(72)28-18-76-75-17-27(56-38(69)24(12-31(60)61)52-40(26)71)39(70)50-21(8-5-9-46-42(44)45)34(65)47-13-29(57)49-23(11-30(58)59)37(68)55-28;3-2(4,5)1(6)7/h2-4,6-7,19,21-28H,5,8-18,43H2,1H3,(H,47,65)(H,48,66)(H,49,57)(H,50,70)(H,51,72)(H,52,71)(H,53,64)(H,54,67)(H,55,68)(H,56,69)(H,58,59)(H,60,61)(H,62,63)(H4,44,45,46);(H,6,7)/t19-,21-,22-,23-,24-,25-,26-,27-,28-;/m0./s1
Chemical Name	2-[(1R,4S,7R,12R,15S,18R,21S,27S)-7-[[(2S)-2-aminopropanoyl]amino]-15-benzyl-4-(carboxymethyl)-12-(carboxymethylcarbamoyl)-27-[3-(diaminomethylideneamino)propyl]-3,6,14,17,20,23,26,29-octaoxo-9,10,31,32-tetrathia-2,5,13,16,19,22,25,28-octazabicyclo[16.11.4]tritriacontan-21-yl]acetic acid;2,2,2-trifluoroacetic acid
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
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	RGD-4C (2.5, 5, 10 μg/mL) suppresses the growth of BAE cells through synthetic form altered by peptides obtained from endostatin[2].
ln Vivo	The B16F10 mouse melanoma is inhibited in vivo in growth by RGD-4C (9.11 mg/kg; injection; single dose)[2]. In a model of muscular invasive bladder cancer, modified RGD-4C fused with the N-terminus of plant-derived single-chain ribosome inactivating protein saporin (SAP) (named RGD-SAP) has anti-tumor efficacy (diluted in sodium chloride, 0.9%; iv; 200 µL; every 5 days, for 3 times)[3]. When RGD-SAP and the chemotherapy medication mitomycin C are combined, mice with orthotopic bladder cancer have a higher chance of survival with no signs of systemic toxicity[3].
References	[1]. Solution structures and integrin binding activities of an RGD peptide with two isomers. Biochemistry. 2001 Feb 27;40(8):2373-8. [2]. Effect of RGD-4C position is more important than disulfide bonds on antiangiogenic activity of RGD-4C modified endostatin derived synthetic polypeptide. Bioconjug Chem. 2010 Jul 21;21(7):1142-7. [3]. A Novel RGD-4C-Saporin Conjugate Inhibits Tumor Growth in Mouse Models of Bladder Cancer. Front Oncol. 2022 Apr 11;12:846958.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.7941 mL	3.9705 mL	7.9410 mL
	5 mM	0.1588 mL	0.7941 mL	1.5882 mL
	10 mM	0.0794 mL	0.3970 mL	0.7941 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.