Cd44v6-derived cyclic peptides for treating cancers and angiogenesis related diseases

Abstract

The present invention relates to compounds, pharmaceutical compositions and methods for treating different forms of cancer and angiogenesis related diseases using cyclic peptides.

What is claimed is: 
     
         1 . A compound comprising:
 a cyclic peptide comprising at least   (a) an amino acid X 1  being selected from the group consisting of the amino acids A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y, further   (b) an amino acid sequence R-W-H, and further   (c) an amino acid X 11  being selected from the group consisting of the amino acids A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y, or a peptidomimetic thereof, or   a cyclic peptide comprising at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein the amino acid X 1  is selected from the group consisting of the amino acids A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y, wherein the amino acids X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 11 , X 12 , X 13  and X 14  are independently selected from the group consisting of the amino acids A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y, and wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 12 , X 13  and X 14  are optionally present in the amino acid sequence, or a peptidomimetic thereof,   the compound comprising a chemical bond between two adjacent amino acids of the cyclic peptide which is not a chemical bond between the N-terminus of a first amino acid and the C-terminus of a second amino acid of the two adjacent amino acids.   
     
     
         2 . The compound of  claim 1 , wherein the amino acid X 1  is an amino acid having an NH 2  group in the amino acid side chain, such as the amino acids K, R, N, or Q, and/or wherein X 2  is optionally present and optionally selected from the group consisting of amino acids with negatively charged side chains such as the amino acid E or D, or amino acids with non-polar side chains such as the amino acids A, V, L or I, wherein X 3  is optionally present and optionally selected from the group consisting of amino acids with an NH 2  group in the amino acid side chain, such as the amino acids K, R, N, or Q, and amino acids with non-polar side chains, such as the amino acids A, V, L or I, wherein X 4  is optionally present and optionally selected from the group consisting of amino acids with non-polar or non-charged side chains and aromatic ring structures, such as the amino acids F, W, or Y, and amino acids with non-polar side chains, such as the amino acids A, V, L or I, wherein X 5  is optionally present and optionally selected from the group consisting of amino acids with non-polar or non-charged side chains and aromatic rings structures, such as the amino acids F, W, or Y, and amino acids with non-polar side chains, such as the amino acids A, V, L or I, wherein X 6  is optionally present and optionally selected from the group consisting of the amino acid G and amino acids with non-polar side chains, such as the amino acids A, V, L or I, wherein X 7  is optionally present and optionally selected from the group consisting of amino acids with an NH 2  group in the side chain, such as the amino acids K, R, N or Q, and amino acids with non-polar side chains, such as the amino acids A, V, L or I, wherein X 11  is selected from the group consisting of amino acids with negatively charged side chains, such as the amino acid E or D, and amino acids with non-polar side chains, such as the amino acids A, V, L or I, wherein X 12  is optionally present and optionally selected from the group consisting of the amino acid G and amino acids with non-polar side chains such as the amino acids A, V, L or I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids with non-polar or non-charged side chains and aromatic rings structures, such the amino acids F, W or Y, and amino acids with non-polar side chains, such as the amino acids A, V, L or I, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids with an NH 2  group in the side chain, such as the amino acids K, R, N or Q, and amino acids with non-polar side chains, such as the amino acids A, V, L or I. 
     
     
         3 . The compound of  claim 1 ,
 wherein X 1  is selected from the group consisting of K, R, N and Q, wherein X 2  is optionally present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and optionally the amino acid E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q.   
     
     
         4 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably the amino acid K, wherein X 2  is optionally present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and the amino acid E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         5 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably the amino acid K, wherein X 2  is optionally present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and the amino acid E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W, and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         6 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N, and Q, preferably the amino acid K, wherein X 2  is optionally present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N, and Q, wherein X 11  is the amino acid E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         7 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably the amino acid K, wherein X 2  is optionally present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is present and optionally selected from the group consisting of amino acids F, W, and Y, wherein X 5  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and optionally E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W, and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         8 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N, and Q, preferably the amino acid K, wherein X 2  is optionally present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  present and is optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and optionally E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         9 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably K, wherein X 2  is present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is present and is optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and optionally the amino acid E or D, wherein X 12  is optionally present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W, and Y and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         10 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably the amino acid K, wherein X 2  is present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is present and is optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is present and is optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and is optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is optionally the amino acid E or D, wherein X 12  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is optionally present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         11 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably the amino acid K, wherein X 2  is present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is present and is optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 11  is present and optionally the amino acid E or D, wherein X 12  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is optionally present and optionally selected from the group consisting of amino acids K, R, N and Q, or a peptidomimetic thereof. 
     
     
         12 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -R-W-H-X 11 -X 12 -X 13 -X 14 , wherein X 1  is present and optionally selected from the group consisting of K, R, N and Q, preferably the amino acid K, wherein X 2  is present and optionally selected from the group consisting of amino acids E and D, wherein X 3  is present and is optionally selected from the group consisting of amino acids K, R, N and Q, wherein X 4  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 5  is present and optionally selected from the group consisting of amino acids F, W and Y, wherein X 6  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 7  is present and optionally selected from the group consisting of amino acids K, R, N, and Q, wherein X 11  is present and optionally the amino acid E or D, wherein X 12  is present and optionally selected from the group consisting of amino acids G, A, V, L and I, wherein X 13  is present and optionally selected from the group consisting of amino acids F, W and Y, and wherein X 14  is present and is optionally selected from the group consisting of amino acids K, R, N, and Q, or a peptidomimetic thereof. 
     
     
         13 . The compound of  claim 1 , wherein X 1  is selected from the group consisting of the amino acids K, R, N, and Q, preferably the amino acid K, wherein X 2 , if present, is selected from the group consisting of amino acids E and D, wherein X 3 , if present, is selected from the group consisting of amino acids K, R, N, and Q, wherein X 4 , if present, is selected from the group consisting of amino acids F, W, and Y, wherein X 5 , if present, is selected from the group consisting of amino acids F, W, and Y, wherein X 6 , if present, is selected from the group consisting of amino acids G, A, V, L and I, wherein X 7 , if present, is selected from the group consisting of amino acids K, R, N, and Q, wherein X 11  is the amino acid D or E, wherein X 12 , if present, is selected from the group consisting of amino acids G, A, V, L and I, wherein X 13 , if present, is selected from the group consisting of amino acids F, W, and Y, and wherein X 14 , if present, is selected from the group consisting of amino acids K, R, N, and Q. 
     
     
         14 . The compound of  claim 1 , wherein X 1  is the amino acid K, wherein X 2 , if present, is the amino acid E, wherein X 3 , if present, is the amino acid Q, wherein X 4 , if present, is the amino acid W, wherein X 5 , if present, is the amino acid F, wherein X 6 , if present, is the amino acid G, wherein X 7 , if present, is the amino acid N, wherein X 11  is the amino acid E, wherein X 12 , if present, is the amino acid G, wherein X 13 , if present, is the amino acid Y, and wherein X 14 , if present, is the amino acid R. 
     
     
         15 . The compound of  claim 1 , wherein the cyclic peptide comprises at least the amino acid sequence X 1 -X 6 -X 7 -R-W-H-X 11 , wherein the amino acid X 1  is selected from the group consisting of the amino acids K, R, N, or Q, preferably X 1  is the amino acid K, wherein the amino acid X 6  is optionally present and selected from the group consisting of amino acids G, A, V, L and I, preferably X 6  is the amino acid G, wherein X 7  is optionally present and selected from a group consisting of amino acids K, R, N, and Q, preferably X 7  is N, and wherein X 11  is the amino acid D or E, preferably X 11  is the amino acid E, or a peptidomimetic thereof, the compound comprising a chemical bond between two adjacent amino acids of the cyclic peptide which is not a chemical bond between the N-terminus of a first amino acid and the C-terminus of a second amino acid of the two adjacent amino acids or the cyclic peptide comprising a chemical bond selected from the group consisting of a chemical bond between an N-terminal amino group of an amino acid and an amino acid side chain, a chemical bond between a C-terminal carboxyl group of an amino acid and an amino acid side chain, and a chemical bond between an amino acid side chain of a first amino acid of the cyclic peptide and an amino acid side chain of a second amino acid of the cyclic peptide. 
     
     
         16 . The compound of  claim 1 , wherein the cyclic peptide comprises, optionally consists of, the amino acid sequence K-R-W-H-E (SEQ ID No.: 34), K-N-R-W-H-E (SEQ ID No.: 35), K-G-N-R-W-H-E (SEQ ID No: 36), or a peptidomimetic thereof. 
     
     
         17 . The compound of  claim 1 , wherein said peptide does not comprise the amino acid sequence N-R-W-H-E (SEQ ID No.: 2), the amino acid sequence K-R-W-H-E and a DOTA modification, the amino acid sequence K-G-N-R-W-H-E-G, the amino acid sequence K-E-Q-W-F-G-N-R-W-H-E-G-Y-R (SEQ ID No.: 6), or a peptidomimetic thereof. 
     
     
         18 . The compound of  claim 1 , wherein the cyclic peptide or peptidomimetic thereof comprises a modification. 
     
     
         19 . The compound of  claim 18 , wherein the modification comprises an amino acid, amino acid derivative, a lipophilic modification, or an aromatic hydrophobic modification, optionally the modification comprises phenyl acetic acid or 3-indole acetic acid. 
     
     
         20 . The compound of  claim 18 , wherein the modification is not DOTA or a myristoyl group. 
     
     
         21 . The compound of  claim 1 , wherein the chemical bond between the two adjacent amino acids involves the amino acid side chain of at least one of said two adjacent amino acids. 
     
     
         22 . The compound of  claim 1 , wherein the cyclic peptide comprises a chemical bond selected from the group consisting of a chemical bond between an N-terminal amino group of an amino acid and an amino acid side chain, a chemical bond between a C-terminal carboxyl group of an amino acid and an amino acid side chain, and a chemical bond between an amino acid side chain of a first amino acid of the peptide and an amino acid side chain of a second amino acid of the peptide. 
     
     
         23 . The compound of  claim 1 , wherein the cyclic peptide comprises a chemical bond selected from the group consisting of a chemical bond between an N-terminal amino group of an amino acid and a carboxyl group of an amino acid side chain, preferably of the amino acids E or D, a chemical bond between a C-terminal carboxyl group of an amino acid and an amino group of an amino acid side chain, preferably of the amino acids K, R, N or Q, and a chemical bond between an amino group of an amino acid side chain of a first amino acid of the peptide, preferably of the amino acids K, R, N or Q, and a carboxyl group of an amino acid side chain of a second amino acid of the peptide, preferably of the amino acids E or D. 
     
     
         24 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence K-R-W-H-E (SEQ ID No.:34), K-N-R-W-H-E (SEQ ID No.: 35) or K-G-N-R-W-H-E (SEQ ID No.: 36), comprising a chemical bond selected from the group consisting of a chemical bond between an N-terminal amino group of an amino acid and an amino acid side chain, optionally a carboxyl group of an amino acid side chain, a chemical bond between a C-terminal carboxyl group of an amino acid and an amino acid side chain, optionally an amino group of an amino acid side chain, and a chemical bond between an amino acid side chain of a first amino acid of the peptide and an amino acid side chain of a second amino acid of the peptide, optionally between a carboxyl group of the amino acid side chain of the first amino acid and an amino group of the amino acid side chain of the second amino acid. 
     
     
         25 . The compound of  claim 23 , wherein the peptide comprises the amino acid sequence K-R-W-H-E (SEQ ID No.: 34) and comprises a chemical bond between an N-terminal amino group of a first amino acid, preferably of the amino acid K, and an amino acid side chain, preferably a carboxyl group of an amino acid side chain, of a second amino acid, preferably of the amino acid E. 
     
     
         26 . The compound of  claim 23 , wherein the peptide comprises the amino acid sequence as depicted in SEQ ID No.: 35 and comprises a chemical bond between an N-terminal amino group of a first amino acid, preferably of the amino acid K, and an amino acid side chain, preferably a carboxyl group of an amino acid side chain, of a second amino acid, preferably of the amino acid E. 
     
     
         27 . The compound of  claim 23 , wherein the peptide comprises the amino acid sequence as depicted in SEQ ID No.: 36 and comprises a chemical bond between an N-terminal amino group of a first amino acid, preferably of the amino acid K, and an amino acid side chain, preferably a carboxyl group of an amino acid side chain, of a second amino acid, preferably of the amino acid E. 
     
     
         28 . The compound of  claim 23 , wherein the peptide comprises the amino acid sequence K-R-W-H-E (SEQ ID No.: 34) and comprises a chemical bond between an amino acid side chain, preferably the amino group of an amino acid side chain, of a first amino acid, preferably of the amino acid K, and the C-terminal carboxyl group of a second amino acid, preferably of E. 
     
     
         29 . The compound of  claim 1 , wherein the amino acid side chain is the amino acid side chain of an amino acid selected from the group consisting of the amino acids E, D, K, R, N and Q. 
     
     
         30 . The compound of  claim 1 , wherein the chemical bond comprises the carboxyl group of an amino acid side chain of an amino acid E or D and/or wherein the chemical bond comprises the amino group of an amino acid side chain of any one of the amino acids K, R, N or Q. 
     
     
         31 . The compound of  claim 1 , wherein the amino acid side chain is modified or truncated. 
     
     
         32 . The compound of  claim 1 , wherein at least one amino acid of the cyclic peptide is a D-amino acid. 
     
     
         33 . The compound of  claim 32 , wherein 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 amino acids are D-amino acids. 
     
     
         34 . The compound of  claim 32 , wherein at least one amino acid of the amino acid sequence R-W-H is a D-amino acid. 
     
     
         35 . The compound of  claim 34 , wherein at least W is a D-amino acid. 
     
     
         36 . The compound of  claim 34 , wherein at least H is a D-amino acid. 
     
     
         37 . The compound of  claim 34 , wherein at least R is a D-amino acid. 
     
     
         38 . The compound of  claim 34 , wherein W is a D-amino acid or wherein R is a D-amino acid, or wherein H is a D-amino acid. 
     
     
         39 . The compound of  claim 34 , wherein the peptide comprises the amino acid sequence K-R-W-H-E (SEQ ID No.: 34), K-N-R-W-H-E (SEQ ID No.: 35) or K-G-N-R-W-H-E (SEQ ID NO.: 36), comprising a chemical bond selected from the group consisting of a chemical bond between an N-terminal amino group of a first amino acid and an amino acid side chain, optionally a carboxyl group of an amino acid side chain, of a second amino acid, a chemical bond between a C-terminal carboxyl group of a first amino acid and an amino acid side chain, optionally an amino group of an amino acid side chain, of a second amino acid, and a chemical bond between an amino acid side chain of a first amino acid of the peptide and an amino acid side chain of a second amino acid of the peptide, optionally between a carboxyl group of the amino acid side chain of the first amino acid and an amino group of the amino acid side chain of the second amino acid, wherein at least one amino acid is a D-amino acid, preferably at least one amino acid of the amino acid sequence R-W-H is a D-amino acid. 
     
     
         40 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence K-R-W-H-E (SEQ ID No.: 34) comprising a chemical bond between an N-terminal amino group of a first amino acid and an amino acid side chain, preferably a carboxyl group of an amino acid side chain, of a second amino acid, preferably comprising a chemical bond between the N-terminal amino group of K and the carboxyl group of the amino acid side chain of E, wherein at least one amino acid is a D-amino acid, preferably at least one amino acid of the amino acid sequence R-W-H is a D-amino acid, preferably the amino acid W is a D-amino acid. 
     
     
         41 . The compound of  claim 1 , wherein the peptide comprises or has the amino acid sequence K-R-W-H-E (SEQ ID No.: 34) and comprises a chemical bond between the N-terminal amino group of the amino acid K and the carboxyl group of the amino acid side chain of the amino acid E, and wherein the amino acid W is a D-amino acid. 
     
     
         42 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence as depicted in SEQ ID No.: 35 and comprises a chemical bond between an N-terminal amino group of a first amino acid, preferably of the amino acid K, and an amino acid side chain, preferably a carboxyl group of an amino acid side chain of a second amino acid, preferably of the amino acid E, wherein at least one amino acid is a D-amino acid. 
     
     
         43 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence as depicted in SEQ ID No.: 36 and comprises a chemical bond between an N-terminal amino group of a first amino acid, preferably of the amino acid K, and an amino acid side chain, preferably a carboxyl group of an amino acid side chain of a second amino acid, preferably of the amino acid E, wherein the amino acid H is a D-amino acid. 
     
     
         44 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence K-R-W-H-E (SEQ ID No.: 34) and comprises a chemical bond between an amino acid side chain, preferably the amino group of an amino acid side chain of a first amino acid, preferably of the amino acid K, and the C-terminal carboxyl group of a second amino acid, preferably of the amino acid E, wherein the amino acid R is a D-amino acid. 
     
     
         45 . The compound of  claim 1 , wherein the peptide is selected from the group consisting of a peptide having the amino acid sequence K-R-W-H-E (SEQ ID No.: 34), comprising a chemical bond between the N-terminal amino group of the amino acid K and the carboxyl group of the amino acid side chain of the amino acid E, and wherein the amino acid W is a D-amino acid, a peptide having the amino acid sequence as depicted in SEQ ID No.: 35, comprising a chemical bond between the N-terminal amino group of the amino acid K and the carboxyl group of the amino acid side chain of the amino acid E, a peptide comprising the amino acid sequence SEQ ID No.: 36, comprising a chemical bond between the N-terminal amino group of the amino acid K and the carboxyl group of the amino acid side chain of the amino acid E, wherein the amino acid H is a D-amino acid, and a peptide comprising the amino acid sequence K-R-W-H-E (SEQ ID No.: 34), comprising a chemical bond between the amino group of the amino acid side chain of the amino acid K and the C-terminal carboxyl group of the amino acid E, wherein the amino acid R is a D-amino acid. 
     
     
         46 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         47 . The compound of  claim 1 , wherein the compound is formulated for intravenous, oral, nasal, or subcutaneous administration. 
     
     
         48 . The compound of  claim 1 , wherein the compound is administered in combination with a cytotoxic compound, an immunopharmaceutical, an antibody against a receptor tyrosine kinase (RTK) and/or a chemotherapeutic agent, preferably the compound of the invention is administered in combination with a compound selected from the group consisting of an epidermal growth factor receptor (EGFR) inhibitor, preferably selected from the group consisting of gefitinib, erlotinib, lapatinib, cetuximab, panitumumab, vandetanib and mixtures thereof, an hepatocyte growth factor receptor (HGF/c-Met) inhibitor, preferably selected from the group consisting of ficlatuzumab, crizotinib, tivantinib, cabozantinib, capmatinib, MGCD265, volitinib, MK8033, MK-2461, and mixtures thereof, a programmed cell death protein 1 (PD-1) inhibitor, preferably selected from the group consisting of nivolumab/BMS-936558, lambrolizumab, pidilizumab, AMP-224, pembrolizumab and mixtures thereof, a programmed death-ligand 1 (PD-L1) inhibitor, preferably selected from the group consisting of BMS-936559, RG7446/MPDL3280A. MEDI4736, MSB0010718C/Avelumab and mixtures thereof, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, preferably ipilimumab, a vascular endothelial growth factor receptor (VEGFR) inhibitors, preferably selected from the group consisting of bevacicumab, pazopanib, sorafenib, sunitinib, axitinib, ponatinib, regorafenib, vandetanib, cabozantinib, lenvatinib, ramucirumab and mixtures thereof, a chemotherapeutic agent, preferably selected from the group consisting of an alkylating agent, preferably selected from the group consisting of a nitrogen mustard, such as mechlorethamine, chlorambucil, cyclophosphamide, ifosfamide and melphalan, nitrosourea, such as streptozocin, carmustine (BCNU) and lomustine, an alkyl sulfonate, such as busulfan, a triazine, such as dacarbazine (DTIC) and temozolomide, an ethylenimine, such as thiotepa and altretamine (hexamethylmelamine), and mixtures thereof, a platinum drug, preferably selected from the group consisting of cisplatin, carboplatin, oxalaplatin and a mixture thereof, an antimetabolite, preferably selected from the group consisting of 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), capecitabine, cytarabine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, pemetrexed, and mixtures thereof, an taxane, an eribulin, folfirinox, folfox, an anthracycline, preferably selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin and a mixture thereof and a mixture thereof and combinations thereof. 
     
     
         49 . The compound of  claim 1  for use as a medicament. 
     
     
         50 . The compound of  claim 1  for use in treating a disease selected from the group consisting of cancer, an angiogenesis related disease, a disease from the field of ophthalmology, diseases associated with an increased invasive potential of cells, and inflammatory disorders in a human being. 
     
     
         51 . The compound of  claim 50 , wherein the cancer is a metastasizing cancer. 
     
     
         52 . The compound of  claim 50 , wherein the disease is selected from the group consisting of estrogen receptor-dependent breast cancer, estrogen receptor-independent breast cancer, hormone receptor-dependent prostate cancer, hormone receptor-independent prostate cancer, brain cancer, renal cancer, colon cancer, familial adenomatous polyposis (FAP), colorectal cancer, pancreatic cancer, bladder cancer, esophageal cancer, stomach cancer, genitourinary cancer, gastrointestinal cancer, uterine cancer, ovarian cancer, astrocytomas, gliomas, skin cancer, squamous cell carcinoma, Keratoakantoma, Bowen disease, cutaneous T-Cell Lymphoma, melanoma, basal cell carcinoma, actinic keratosis; ichtiosis; acne, acne vulgaris, sarcomas, Kaposi's sarcoma, osteosarcoma, head and neck cancer, small cell lung carcinoma, non-small cell lung carcinoma, leukemia, lymphomas and/or other blood cell cancers, thyroid resistance syndrome, diabetes, thalassemia, cirrhosis, protozoal infection, rheumatoid arthritis, rheumatoid spondylitis, all forms of rheumatism, osteoarthritis, gouty arthritis, multiple sclerosis, insulin dependent diabetes mellitus, non-insulin dependent diabetes, asthma, rhinitis, uveithis, lupus erythematoidis, ulcerative colitis, Morbus Crohn, inflammatory bowel disease, chronic diarrhea, psoriasis, atopic dermatitis, bone disease, fibroproliferative disorders, atherosclerosis, aplastic anemia, DiGeorge syndrome, Graves' disease, epilepsia, status epilepticus, alzheimer's disease, depression, schizophrenia, schizoaffective disorder, mania, stroke, mood-incongruent psychotic symptoms, bipolar disorder, affective disorders, meningitis, muscular dystrophy, multiple sclerosis, agitation, cardiac hypertrophy, heart failure, reperfusion injury, diabetic retinopathy, age-related macular degeneration, allergic diseases, e.g. asthma, due to an increase in eosinophil granulocytes, rejection of heart transplantation, and obesity in a human being. 
     
     
         53 . The compound of  claim 50 , wherein said cancer shows expression of CD44v6. 
     
     
         54 . The compound of a  claim 50 , wherein said cancer is classifiable as Stage III or Stage IV according to the TNM anatomic/prognostic group system of the cancer staging system of the American Joint Committee on Cancer. 
     
     
         55 . The compound of  claim 50 , wherein said cancer is classifiable as Stage IV according to the TNM anatomic/prognostic group system of the cancer staging system of the American Joint Committee on Cancer. 
     
     
         56 . The compound of  claim 50 , wherein said cancer is a metastasizing cancer selected from the group consisting of metastasizing forms of Hodgkin lymphoma, colorectal cancer, cervical cancer, lung cancer, skin cancer such as squamous cell cancer or basal cell carcinoma, head and neck cancer, gastric cancer, pancreatic cancer, head and neck squamous cell cancer, and breast cancer. 
     
     
         57 . The compound of  claim 50 , wherein said cancer is a metastasizing cancer selected from the group consisting of metastasizing forms of Hodgkin lymphoma, colorectal cancer, cervical cancer, lung cancer, skin cancer such as squamous cell cancer or basal cell carcinoma, head and neck cancer, gastric cancer, pancreatic cancer, and breast cancer, wherein said metastasizing cancer is classifiable as Stage IV according to the TNM anatomic/prognostic group system of the cancer staging system of the American Joint Committee on Cancer, and wherein said metastasizing cancer shows expression of CD44v6.