iRGD peptide (sequence: CRGDKGPDC) is a 9-amino acid cyclic peptide, and a molecular mimicry agent that was originally identified in an in vivo screening of phage display libraries in tumor-bearing mice. It triggers tissue penetration of drugs by first binding to av integrins, then proteolytically cleaved in the tumor to produce CRGDK/R to interact with neuropilin-1, and has tumor-targeting and tumor-penetrating properties. The peptide was able to home to tumor tissues, but in contrast to standard RGD (Arginylglycylaspartic acid) peptides, also spread much more extensively into extravascular tumor tissue. It was later identified that this extravasation and transport through extravascular tumor tissue was due to the bifunctional action of the molecule: after the initial RGD-mediated tumor homing, another pharmacological motif is able to manipulate tumor microenvironment, making it temporarily accessible to circulating drugs. This second step is mediated through specific secondary binding to neuropilin-1 receptor, and subsequent activation of a trans-tissue pathway, dubbed the C-end Rule (CendR) pathway.
Physicochemical Properties
| Molecular Formula | C35H57N13O14S2 |
| Molecular Weight | 948.035784482956 |
| Exact Mass | 947.358 |
| CAS # | 1392278-76-0 |
| PubChem CID | 134611625 |
| Appearance | White to off-white solid powder |
| LogP | -11.3 |
| Hydrogen Bond Donor Count | 14 |
| Hydrogen Bond Acceptor Count | 19 |
| Rotatable Bond Count | 13 |
| Heavy Atom Count | 64 |
| Complexity | 1750 |
| Defined Atom Stereocenter Count | 7 |
| SMILES | S1CC(C(=O)O)NC(C(CC(=O)O)NC(C2CCCN2C(CNC(C(CCCCN)NC(C(CC(=O)O)NC(CNC(C(CCC/N=C(\N)/N)NC(C(CS1)N)=O)=O)=O)=O)=O)=O)=O)=O |
| InChi Key | YHTTWXCDIRTOQX-FQJIPJFPSA-N |
| InChi Code | InChI=1S/C35H57N13O14S2/c36-8-2-1-5-18-30(57)42-14-25(50)48-10-4-7-23(48)33(60)46-21(12-27(53)54)32(59)47-22(34(61)62)16-64-63-15-17(37)28(55)44-19(6-3-9-40-35(38)39)29(56)41-13-24(49)43-20(11-26(51)52)31(58)45-18/h17-23H,1-16,36-37H2,(H,41,56)(H,42,57)(H,43,49)(H,44,55)(H,45,58)(H,46,60)(H,47,59)(H,51,52)(H,53,54)(H,61,62)(H4,38,39,40)/t17-,18-,19-,20-,21-,22-,23-/m0/s1 |
| Chemical Name | (6S,9S,15S,18R,23R,26S,29S)-18-amino-6-(4-aminobutyl)-9,26-bis(carboxymethyl)-15-[3-(diaminomethylideneamino)propyl]-2,5,8,11,14,17,25,28-octaoxo-20,21-dithia-1,4,7,10,13,16,24,27-octazabicyclo[27.3.0]dotriacontane-23-carboxylic 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | Three processes are involved in iRGD peptide-mediated tumor penetration: first, it binds to αv-integrins on tumor vasculature or tumor cells; second, it exposes a C-terminal motif that binds to neuropilin-1 (NRP-1); and third, it internalizes the cell. The insertion of an iRGD peptide into the C terminus of the ICOVIR15K fiber only improves binding and internalization in MCF7 cells that express integrins and NRP-1. Viral infection and replication are unaffected by iRGD insertion[1]. When coupled with 5-FU, iRGD peptide (0.3 μmol/mL) increases the chemotherapeutic efficacy of 5-FU on gastric cancer cells through NRP1[2]. However, iRGD peptide alone has no discernible effect on gastric cancer cells. |
| ln Vivo | When iRGD is introduced into the oncolytic adenovirus ICOVIR15K, the result is an increased anticancer effect in mice as well as improved early viral diffusion into the tumor mass[1]. When 5-FU is combined with iRGD (4 mmol/kg, iv), it considerably slows down the formation of tumors in nude mice that are harboring human stomach cancer cells[2]. |
| References |
[1]. iRGD tumor-penetrating peptide-modified oncolytic adenovirus shows enhanced tumor transduction, intratumoral dissemination and antitumor efficacy. Gene Ther. 2014 Aug;21(8):767-74. [2]. Combination of NRP1-mediated iRGD with 5-fluorouracil suppresses proliferation, migration and invasion of gastric cancer cells. Biomed Pharmacother. 2017 Sep;93:1136-1143. |
| Additional Infomation | Internalized-arginylglycylaspartic Acid Cyclic Peptide is a 9 amino acid-based cyclic, tumor specific homing, arginine-glycine-aspartic acid (RGD)-based peptide (CRGDKRGPDC), with tumor penetrating activity. The iRGD contains the RGD motif as well as the C-terminal end binding (CendR) motif that increases internalization. Upon administration, the RGD motif of the iRGD peptide is able to specifically target tumors by binding to alphavbeta3/alphavbeta5 integrins on tumor endothelium. In turn, iRGD is cleaved by specific tumor proteases, which exposes the positively charged CendR motif. This motif binds to neuropilin-1 (NRP-1), a receptor overexpressed on certain tumor cells. This increases vascular permeability of tumor blood vessels and promotes tumor penetration. Compared to other RGD peptides, this agent is able to both improve delivery and increase the accumulation of co-administered or conjugated chemotherapeutic agents in the tumor. |
Solubility Data
| Solubility (In Vitro) | H2O : ≥ 50 mg/mL (~52.74 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (105.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0548 mL | 5.2740 mL | 10.5481 mL | |
| 5 mM | 0.2110 mL | 1.0548 mL | 2.1096 mL | |
| 10 mM | 0.1055 mL | 0.5274 mL | 1.0548 mL |