Agonists of guanylate cyclase useful for downregulation of pro-inflammatory cytokines
OwnerKunwar SHAILUBHAIinventor
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Abstract
This invention provides a method to prevent, control, and/or treat an inflammatory disease or disorder by administering at least one agonist of guanalyte cyclase receptor, or pharmaceutical compositions thereof, either alone or either concurrently or sequentially with another compound or an active agent used to treat the disease or disorder, and/or with an inhibitor of cGMP-dependent phosphodieasterases.
Claims25
A composition comprising a guanylate cyclase receptor agonist (GCRA) peptide comprising of the sequence of any one of Tables 1-7 and a NF-κB inhibitor, a c-Src tyrosine kinase inhibitor, a 5-ASA agent, a c-Myc inhibitor, or an Ikk inhibitor.
A method for preventing or treating a condition selected from the group consisting of colitis, ulcerative colitis, Crohn's disease, irritable bowel syndrome (IBS), non-ulcer dyspepsia, chronic intestinal pseudo-obstruction, functional dyspepsia, colonic pseudo-obstruction, duodenogastric reflux, constipation, constipation associated with use of opiate pain killers, post-surgical constipation, IBS-associated constipation, constipation associated with neuropathic disorders, gastroesophageal reflux disease (GERD), Celiac disease, gastroparesis, heartburn, poor gastrointestinal motility, congestive heart failure, hypertension, benign prostatic hyperplasia (BPH), gastrointestinal cancer, lung cancer, bladder cancer, liver cancer, salivary gland cancer, skin cancer, bronchitis, tissue inflammation, organ inflammation, respiratory inflammation, asthma, COPD, lipid metabolism disorder, biliary disorder, cardiovascular disease, obesity and an endocrine disorder comprising administering to a subject in need thereof a therapeutically effective amount of a composition of comprising a GCRA peptide recited in any of one Tables 1-7.
A method of treating or alleviating a symptom of a NF-κB mediated inflammation comprising administering to a subject in need thereof an effective amount of a GCRA peptide or pharmaceutical composition thereof or the composition comprising a GCRA peptide recited in any of one Tables 1-7, wherein the effective amount is sufficient to inhibit NF-κB activation.
A method of modulating NF-κB induction in a cell comprising contacting the cell with an effective amount of a GCRA peptide or pharmaceutical composition thereof or the composition comprising a GCRA peptide recited in any of one Tables 1-7.
A method of modulating NF-κB-dependent target gene expression in a cell comprising contacting the cell with an effective amount of a GCRA peptide or pharmaceutical composition thereof or the composition comprising a GCRA peptide recited in any of one Tables 1-7, wherein the effective amount is sufficient to inhibit NF-κB activation.
The method of claim 16, wherein said GCRA peptide is SP304 (SEQ ID NO:
- 1), SP333 (SEQ ID NO.:9), or SP373 (SEQ ID NO:
- 250).
Dependencies are inferred from the claim text.