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AssigneeMedical College of Georgia Research Institute, Inc. Georgia
InventorsVadivel Ganapathy, Puttur D. Prasad, Muthusamy Thangaraju, Gail Cresci
Estimating the term…
Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR 109 ligands include, but are not limited to butyrate, β-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2′-deoxytidine, 1-β-D-arabinfαmosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR 109 ligand serum blood level of about 1 to about 1000 μM. The compositions are useful for the treatment of one or more symptoms of cancer. Preferred cancers that can be treated using the disclosed compositions include, but are not limited to colon cancer, breast cancer and leukemia. Methods for treating cancer, inflammatory disorders, and diarrhea are also provided.
A pharmaceutical composition comprising an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methylase inhibitor to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control.
A method for treating one or more symptoms of cancer comprising administering to a subject an effective amount DNA methyltransferase inhibitor to induce expression of GPR109 in the subject and subsequently administering an effective amount of a GPR109 ligand to promote apoptosis of the cells induced to express GPR109.
A method for treating an inflammatory disorder comprising administering to a subject an effective amount of a GPR109 ligand to reduce intracellular cAMP in the subject.
A method for treating diarrhea comprising administering to a subject an effective amount of a GPR109 ligand to decrease intracellular cAMP levels in intestinal epithelial cells of the subject.
Dependencies are inferred from the claim text.