α4β7 peptide monomer and dimer antagonists
First Claim
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1. A method for treating an inflammatory bowel disease in a subject, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising a peptide dimer compound comprising two monomer subunits, wherein each monomer subunit comprises the amino acid sequence:
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Pen-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β
-homo-Glu)-(D-Lys),or a pharmaceutically acceptable salt thereof,and wherein the two monomer subunits are linked by a linker moiety.
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Abstract
The invention relates to peptide dimer compounds and peptide monomer compounds that potently inhibit binding of α4β7 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, possess high selectivity against α4β1 binding, and have high stability under gastrointestinal conditions.
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Citations
14 Claims
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1. A method for treating an inflammatory bowel disease in a subject, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising a peptide dimer compound comprising two monomer subunits, wherein each monomer subunit comprises the amino acid sequence:
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Pen-(N-Me-Arg)-Ser-Asp-Thr-Leu-Pen-Phe(4-tBu)-(β
-homo-Glu)-(D-Lys),or a pharmaceutically acceptable salt thereof, and wherein the two monomer subunits are linked by a linker moiety. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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11. The method of claim 1, wherein the peptide dimer compound or pharmaceutically acceptable salt thereof is an acetate salt of the peptide dimer compound.
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12. The method of claim 10, wherein the peptide dimer compound or pharmaceutically acceptable salt thereof is an acetate salt of the peptide dimer compound.
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13. The method of claim 1, wherein the inflammatory bowel disease is Crohn'"'"'s disease.
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14. The method of claim 1, wherein the inflammatory bowel disease is microscopic colitis.
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