SUBSTRATES AND INHIBITORS OF PROLYL OLIGOPEPTIDASE AND FIBROBLAST ACTIVATION PROTEIN AND METHODS OF USE

摘要

Inhibitors of fibroblast activation protein alpha (FAP) and Prolyl Oligopeptidase (POP) are disclosed, along with their use in various therapies related to conditions, diseases, and disorders involving abnormal cell proliferation such as malignancies and angiogenesis, and in neural disorders such as Alzheimer's disease. Stalk portions of the inhibitor molecules, and substrates of FAP and POP, are also disclosed and may be used, for example, in screening methods for identifying such inhibitors.

主权项

1. A compound having the formula:
B-Xaa1a-Sp-Xaa2a-Cyc  (Formula II), wherein: B is at least one of aminobenzoyl (Abz), acetyl (Ac), benzoyl (Bz), benzyloxycarbonyl (Z), τ-Butyloxycarbonyl (Boc), Furylacryloyl (Fa), Methoxysuccinyl (MeOSuc), Pyroglutamate (Pyr), Pyrazine, Phenylalanine, and Succinyl (Suc); Xaa1a is a positively-charged or negatively-charged amino-acid; Sp is a spacer molecule having a length in the range of 0.3 nm to 2.5 nm; Xaa2a is a positively-charged amino acid; and Cyc is a boronyl proline, proline carbonitrile, nitrile pyrrolidone, or cyanopyrrolidine.