Peptide name : RP7

Source/Organism : RAGE(receptor for advanced glycation end product) inhibitor

Linear/Cyclic : Linear

Chirality : L

Peptide length: 7

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTT assay

Assay time : 48-h

Activity : IC50 = 29.9 µM

Cell line : BT-549

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 822.8691 Dalton

Aliphatic index : 0.142

Instability index : 63.6

Hydrophobicity (GRAVY) : -2.171

Isoelectric point : 9.8004

Charge (pH 7) : 0.883

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 0.4

hydrophobic moment : 1.0651

Missing amino acid : C,D,E,F,G,I,K,L,M,S,V,W,Y

Most occurring amino acid : A

Most occurring amino acid frequency : 1

Least occurring amino acid : A

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (14., 28., 14.)

SMILES Notation: C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)O)[C@@H](C)O

1 : Dai X, et al. A specific RAGE-binding peptide inhibits triple negative breast cancer growth through blocking of Erk1/2/NF-κB pathway. Eur J Pharmacol. 2023; 954:175861. doi: 10.1016/j.ejphar.2023.175861

Paper title : A specific RAGE-binding peptide inhibits triple negative breast cancer growth through blocking of Erk1/2/NF-κB pathway.

Doi : https://doi.org/10.1016/j.ejphar.2023.175861

Abstract : Triple-negative breast cancer (TNBC) is an aggressive cancer that poses a significant threat to women's health. Unfortunately, the lack of clinical targets leads the poor clinical outcomes in TNBC. Many cancers demonstrate overexpression of receptor for advanced glycation end products (RAGE), which can contribute to cancer progression. Despite the potential therapeutic value of blocking RAGE for TNBC treatment, effective peptide drugs have yet to be developed. In our study, we observed that RAGE was highly expressed in TNBC and was associated with poor disease progression. We subsequently investigated the antitumor effects and underlying mechanisms of the RAGE antagonist peptide RP7 in both in vitro and in vivo models of TNBC. Our study revealed that RP7 selectively binds to RAGE-overexpressing TNBC cell lines, including MDA-MB-231 and BT549, and significantly inhibits cell viability, migration, and invasion in both cell lines. Furthermore, RP7-treatment suppressed tumor growth in TNBC xenograft mouse models without inducing detectable toxicity in normal tissues. Mechanistically, RP7 was found to inhibit the phosphorylation of ERK1/2, IKKα/β, IKBα, and p65 to block the NF-κB pathway, prevent the entry of p65 into the nucleus, decrease the protein expression of Bcl-2 and HMGB1, and promote the release of cytochrome C from the mitochondria into the cytoplasm. These effects were observed to activate apoptosis and inhibit epithelial-mesenchymal transition (EMT) in TNBC cells. This study highlights RAGE as a candidate therapeutic target for TNBC treatment and suggests that the RAGE antagonist peptide RP7 is a promising anticancer drug for TNBC.