Oral peptide inhibitors of interleukin-23 receptor and their use to treat inflammatory bowel diseases
AssigneeProtagonist Therapeutics, Inc.
InventorsAshok BHANDARI, Gregory Thomas BOURNE, Xiaoli CHENG, Brian Troy FREDERICK, Jie ZHANG, Dinesh V. PATEL, David LIU
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Abstract
Peptide inhibitors of the interleukin-23 receptor, and related compositions and methods of using these peptide inhibitors to treat or prevent a variety of diseases and disorders, including inflammatory bowel disease, are disclosed.
Claims54
A peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of Formula (Xa):
- (Xa)
- X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-
- X15-X16-X17-X18-X19-X20
- wherein
- X1 is any amino acid or absent;
- X2 is any amino acid or absent;
- X3 is any amino acid or absent;
- X4 is any amino acid or chemical moiety capable of forming a bond with X9;
- X5 is any amino acid;
- X6 is any amino acid;
- X7 is any amino acid;
- X8 is any amino acid;
- X9 is any amino acid or chemical moiety capable of forming a bond with X4;
- X10 is any amino acid;
- X11 is any amino acid;
- X12 is any amino acid;
- X13 is any amino acid;
- X14 is any amino acid;
- X15 is any amino acid,
- X16 is any amino acid or absent;
- X17 is any amino acid or absent;
- X18 is any amino acid or absent;
- X19 is any amino acid or absent;
- and
- X20 is any amino acid or absent,
- wherein the peptide inhibitor is cyclized via a bond between X4 and X9, and
- wherein the peptide inhibitor inhibits the binding of an interleukin-23 (IL-23) to an IL-23 receptor.
A method of assessing the ability of a candidate compound to inhibit or reduce an inflammatory disease or disorder, comprising:
- (a) providing to a rat an amount of dextran sulfate sodium (DSS) or 2,4,6-Trinitrobenzenesulfonic acid (TNBS) sufficient to induce an inflammatory bowel disease (IBD);
- (b) providing to the rat an amount of a candidate compound;
- and
- (c) measuring an amount of IBD symptoms present in the rat after being provided with the DSS and the candidate compound;
- wherein if the amount of IBD symptoms measured in (c) are significantly lower than the amount measured in a control rat provided with the amount of DSS or TNBS and either an amount of a control compound or no peptide (e.g., vehicle control), the candidate compound inhibits or reduces the inflammatory disease or disorder.
Dependencies are inferred from the claim text.