Peptide name : LUNA18

Source/Organism : Synthetic

Linear/Cyclic : Cyclic

Chirality : L

Peptide length: Not available

C-terminal modification: Cyclic

N-terminal modification : Free

Non-natural peptide information:

Assay type : CellTiter-Glo Cell Viability assay

Assay time : Not available

Activity : IC50 = 2.7 ± 0.4 nmol/L

Cell line : LS 180

Cancer type : Colon Cancer

Other activity : Anticancer and Antitumor

Amino Acid Composition Bar Chart : Not available

Molecular mass : Not available

Aliphatic index : Not available

Instability index : Not available

Hydrophobicity (GRAVY) : Not available

Isoelectric point : Not available

Charge (pH 7) : Not available

Aromaticity : Not available

Molar extinction coefficient (cysteine, cystine): Not available

Hydrophobic/hydrophilic ratio : Not available

hydrophobic moment : Not available

Missing amino acid : Not available

Most occurring amino acid : Not available

Most occurring amino acid frequency : Not available

Least occurring amino acid : Not available

Least occurring amino acid frequency : Not available

3D-structure: Not available

Secondary structure fraction (Helix, Turn, Sheet): Not available

SMILES Notation: Not available

Molecular descriptors: Not available

ADMET properties: Not available

1 : Ohta A, et al. Validation of a New Methodology to Create Oral Drugs beyond the Rule of 5 for Intracellular Tough Targets. J Am Chem Soc. 2023; 145:24035-24051. doi: 10.1021/jacs.3c07145

Paper title : Validation of a New Methodology to Create Oral Drugs beyond the Rule of 5 for Intracellular Tough Targets.

Doi : https://doi.org/10.1021/jacs.3c07145

Abstract : Establishing a technological platform for creating clinical compounds inhibiting intracellular protein-protein interactions (PPIs) can open the door to many valuable drugs. Although small molecules and antibodies are mainstream modalities, they are not suitable for a target protein that lacks a deep cavity for a small molecule to bind or a protein found in intracellular space out of an antibody's reach. One possible approach to access these targets is to utilize so-called middle-size cyclic peptides (defined here as those with a molecular weight of 1000-2000 g/mol). In this study, we validated a new methodology to create oral drugs beyond the rule of 5 for intracellular tough targets by elucidating structural features and physicochemical properties for drug-like cyclic peptides and developing library technologies to afford highly N-alkylated cyclic peptide hits. We discovered a KRAS inhibitory clinical compound (LUNA18) as the first example of our platform technology.