Peptide name : ATX-101

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 25

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : CCK-8 assay

Assay time : 96-h

Activity : IC50 = 4.9 ± 0.3 μM

Cell line : U-251

Cancer type : Brain Tumor

Other activity : Antitumor and Cell Penetrating

Amino acid composition bar chart :

Molecular mass : 3633.4403 Dalton

Aliphatic index : 0.428

Instability index : 272.044

Hydrophobicity (GRAVY) : -2.756

Isoelectric point : 12

Charge (pH 7) : 16.4964

Aromaticity : 8

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

Hydrophobic/hydrophilic ratio : 0.3158

hydrophobic moment : 0.1491

Missing amino acid : A,C,E,F,G,H,N,P,Q,S,T,Y

Most occurring amino acid : R

Most occurring amino acid frequency : 13

Least occurring amino acid : M

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (28, 4, 20)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](N)CCSC)C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O

1 : Gravina GL, et al. ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma. Cancers (Basel). 2022; 14:(unknown pages). doi: 10.3390/cancers14020289

Paper title : ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma.

Doi : https://doi.org/10.3390/cancers14020289

Abstract : Cell proliferation requires the orchestrated actions of a myriad of proteins regulating DNA replication, DNA repair and damage tolerance, and cell cycle. Proliferating cell nuclear antigen (PCNA) is a master regulator which interacts with multiple proteins functioning in these processes, and this makes PCNA an attractive target in anticancer therapies. Here, we show that a cell-penetrating peptide containing the AlkB homolog 2 PCNA-interacting motif (APIM), ATX-101, has antitumor activity in a panel of human glioblastoma multiforme (GBM) cell lines and patient-derived glioma-initiating cells (GICs). Their sensitivity to ATX-101 was not related to cellular levels of PCNA, or p53, PTEN, or MGMT status. However, ATX-101 reduced Akt/mTOR and DNA-PKcs signaling, and a correlation between high Akt activation and sensitivity for ATX-101 was found. ATX-101 increased the levels of γH2AX, DNA fragmentation, and apoptosis when combined with radiotherapy (RT). In line with the in vitro results, ATX-101 strongly reduced tumor growth in two subcutaneous xenografts and two orthotopic GBM models, both as a single agent and in combination with RT. The ability of ATX-101 to sensitize cells to RT is promising for further development of this compound for use in GBM.