Novel inhibitors of kallikrein proteases and uses thereof

The present invention relates to a cyclic inhibitor of a kallikrein protease comprising or consisting of (I) the peptide (X1 (X2)(X3)R(X4)(X5)(X6)(X7)(X8)(X9)(X10)(X11) (Formula (X)), wherein (X1) is present or absent and, is preferably present, and if present, is an amino acid, and is most preferably D-alanine or G; (X2) is an amino acid with a side chain; (X3) is an amino acid with a polar uncharged side chain, is preferably with a polar uncharged side chain comprising a hydroxyl group, is more preferably T or S and is most preferably T; (X4) is an amino acid, preferably citrulline, Q or E; (X5) is an amino acid, preferably an amino acid with a hydrophobic side chain; (X6) is present or absent, is preferably absent, and, if present, is an amino acid with a negatively charged side chain, preferably D; (X7) is present or absent, is preferably present, and, if present, is an amino acid, more preferably an amino acid with a side chain comprising a pyrrole of indole, even more preferably P, hydroxyl-proline, (R)-3- piperidine carboxylic acid or W, and most preferably P; (X8) is present or absent and, if present, is an amino acid, and is preferably absent; (X9) is present or absent and, if present, is an amino acid, and is preferably absent; (X10) is an amino acid with a side chain; and (X11) is present or absent and, if present, is an amino acid, and is preferably absent; wherein the side chains of (X2) and (X10) are connected via a connecting molecule, said connecting molecule having at least two functional groups, each functional group forming a covalent bond with one of the side chains of (X2) and (X10); and wherein the kallikrein protease is Kallikrein-related peptidase (KLK5); or (II) the peptide (Y1)(Y2)(Y3)(Y4)(Y5)(Y6)(Y7)(Y8)(Y9) (Formula (Y)), wherein (Y1) is present or absent, is preferably present, and, if present, is an amino acid, preferably P, L-beta-hydroxyl-proline, D-proline, (R)-3-piperidine carboxylic acid, Q or R, and is most preferably P; (Y2) is an amino acid with a side chain; (Y3) is I, L or L- Neopentylglycine, and is preferably L; (Y4) is Y or F, and is preferably Y; (Y5) is an amino acid, preferably an amino acid with a hydrophobic side chain, or Q or R, is more preferably L, norleucine, Q, I, R or M, and is most preferably norleucine or L; (Y6) is an amino acid, preferably an amino acid with a hydrophobic side chain and is most preferably A; (Y7) is absent or present, preferably present and, if present, is an amino acid preferably Q, homoarginine, 4-guanidino-phenlalanine or R; (Y8) is an amino acid with a side chain; and (Y9) is present or absent and, if present, is an amino acid, preferably S, and is most preferably absent; wherein the side chains of (Y2) and (Y8) are connected via a connecting molecule, said connecting molecule having at least two functional groups, each functional group forming a covalent bond with one of the side chains of (Y2) and (Y8); and wherein the kallikrein protease is Kallikrein-related pepti