JP-2022515721-A5 -

Dates

Publication Date

20221219

Application Date

20191213

Description

The peptide ligand of the present invention was tested using the FAPα binding and FAPα enzyme inhibition assays described above. The results are shown in Table 1: Table 1: Biological assay data of the peptide ligand of the present invention This application provides the invention in the following embodiments. (Aspect 1) A peptide ligand specific to FAPα, comprising a polypeptide containing at least three cysteine residues separated by at least two loop sequences, and a molecular scaffold that forms covalent bonds with the cysteine residues of the polypeptide, thereby forming at least two polypeptide loops on the molecular scaffold. (Aspect 2) The peptide ligand according to embodiment 1, wherein the loop sequence comprises 2, 6, or 7 amino acids. (Aspect 3) The peptide ligand according to embodiment 1 or embodiment 2, wherein the loop sequence comprises three cysteine residues separated by two loop sequences, both of which consist of six amino acids. (Aspect 4) The peptide ligand according to embodiment 1 or embodiment 2, wherein the loop sequence comprises three cysteine residues separated by two loop sequences, one of which consists of two amino acids and the other of which consists of seven amino acids. (Aspect 5) The peptide ligands are: SEQ ID NOs: 1-4 (Chem.1) (Here, Ci , Ciii , and Ciiii represent the first, second, and third cysteine residues, respectively.) A peptide ligand according to embodiment 1 or embodiment 2, comprising an amino acid sequence selected from any one of the following or a pharmaceutically acceptable salt thereof. (Aspect 6) The peptide ligand, A-(Sequence ID 1)-A; A - (Sequence ID 2) - A; A-(Sequence ID 3)-A; and A-(Sequence No. 4)-A A peptide ligand according to embodiment 5, comprising an amino acid sequence selected from: (Aspect 7) The peptide ligand is A-(Sequence ID 1)-A; and A-(Sequence No. 3)-A A peptide ligand according to embodiment 6, comprising an amino acid sequence selected from: (Appendix 8) The peptide ligand according to any one of embodiments 1 to 7, wherein the pharmaceutically acceptable salt is selected from free acids or sodium, potassium, calcium, and ammonium salts. (Aspect 9) The peptide ligand according to any one of embodiments 1 to 8, wherein the FAPα is human FAPα. (Aspect 10) A drug conjugate comprising a peptide ligand according to any one of embodiments 1 to 9, conjugated to one or more effectors and/or functional groups. (Phenomenon 11) A pharmaceutical composition comprising a peptide ligand according to any one of embodiments 1 to 9 or a drug conjugate according to embodiment 10 in combination with one or more excipients that are acceptable as pharmaceuticals. (Aspect 12) A peptide ligand according to any one of embodiments 1 to 9 or a drug conjugate according to embodiment 10 for use in the prevention, suppression, or treatment of diseases or disorders mediated by FAPα.