α4β7 thioether peptide dimer antagonists
The invention relates to thioether monomer and dimer peptide molecules which inhibit binding of α4β7 to the mucosal addressing cell adhesion molecule (MAdCAM) in vivo.
1. A method for treating or preventing an Inflammatory Bowel Disease (IBD) in a subject in need thereof, the method comprising providing to the subject an effective amount of a peptide dimer compound comprising two peptides, or a pharmaceutically acceptable salt thereof, wherein each of the two peptides comprises the sequence:
(SEQ ID NO: 270)
2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-
Phe(4-tBu)-(β-homo-Glu)-(D-Lys);
wherein each of the two peptides comprises a thioether bond between the 2-methylbenzoyl and the Pen; and
wherein the two peptides are linked by a linker moiety.
2. The method of claim 1 , wherein the linker moiety is bound to the D-Lys of each of the two peptides.
3. The method of claim 1 , wherein the linker moiety is diglycolic acid (DIG).
4. The method of claim 1 , wherein each of the two peptides comprises the sequence:
(SEQ ID NO: 223)
2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-
Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH.
5. The method of claim 1 , wherein each of the two peptides consists of the sequence:
(SEQ ID NO: 223)
2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-
Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-OH.
6. The method of claim 1 , wherein each of the two peptides comprises the sequence:
(SEQ ID NO: 222)
2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-
Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-NH 2 .
7. The method of claim 1 , wherein each of the two peptides consists of the sequence:
(SEQ ID NO: 222)
2-methylbenzoyl-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-
Phe(4-tBu)-(β-homo-Glu)-(D-Lys)-NH 2 .
8. The method of claim 1 , wherein peptide dimer compound or pharmaceutically acceptable salt thereof is an acetate salt of the peptide dimer compound.
9. The method of claim 1 , wherein the IBD is ulcerative colitis.
10. The method of claim 1 , wherein the IBD is Crohn's disease.
11. The method of claim 1 , wherein the peptide molecule is administered orally.
12. The method of claim 5 , wherein the IBD is ulcerative colitis.
13. The method of claim 5 , wherein the IBD is Crohn's disease.
14. The method of claim 5 , wherein the peptide molecule is administered orally.
15. The method of claim 7 , wherein the IBD is ulcerative colitis.
16. The method of claim 7 , wherein the IBD is Crohn's disease.
17. The method of claim 7 , wherein the peptide molecule is administered orally.