Peptide name : ST101

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : D

Peptide length: 38

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : Annexin V/ PI staining assay

Assay time : 48-h

Activity : mean EC50 value of 2.1 ± 0.4 μmol/L

Cell line : MCF-7

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 4724.459 Dalton

Aliphatic index : 0

Instability index : 40.1684

Hydrophobicity (GRAVY) : -1.205

Isoelectric point : 10.866

Charge (pH 7) : 4.7468

Aromaticity : 7.894

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

Hydrophobic/hydrophilic ratio : infinite

hydrophobic moment : 0

Missing amino acid : A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y

Most occurring amino acid : r

Most occurring amino acid frequency : 7

Least occurring amino acid : v

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (55., 7.8, 26.)

SMILES Notation: CSCC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O

1 : Darvishi E, et al. Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β. Mol Cancer Ther. 2022; 21:1632-1644. doi: 10.1158/1535-7163.MCT-21-0962

Paper title : Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β.

Doi : https://doi.org/10.1158/1535-7163.MCT-21-0962

Abstract : CCAAT/enhancer binding protein β (C/EBPβ) is a basic leucine zipper (bZIP) family transcription factor, which is upregulated or overactivated in many cancers, resulting in a gene expression profile that drives oncogenesis. C/EBPβ dimerization regulates binding to DNA at the canonical TTGCGCAA motif and subsequent transcriptional activity, suggesting that disruption of dimerization represents a powerful approach to inhibit this previously "undruggable" oncogenic target. Here we describe the mechanism of action and antitumor activity of ST101, a novel and selective peptide antagonist of C/EBPβ that is currently in clinical evaluation in patients with advanced solid tumors. ST101 binds the leucine zipper domain of C/EBPβ, preventing its dimerization and enhancing ubiquitin-proteasome dependent C/EBPβ degradation. ST101 exposure attenuates transcription of C/EBPβ target genes, including a significant decrease in expression of survival, transcription factors, and cell-cycle-related proteins. The result of ST101 exposure is potent, tumor-specific in vitro cytotoxic activity in cancer cell lines including glioblastoma, breast, melanoma, prostate, and lung cancer, whereas normal human immune and epithelial cells are not impacted. Further, in mouse xenograft models ST101 exposure results in potent tumor growth inhibition or regression, both as a single agent and in combination studies. These data provide the First Disclosure of ST101, and support continued clinical development of ST101 as a novel strategy for targeting C/EBPβ-dependent cancers.