Abstract: The present disclosure relates generally to methods of preventing, reducing risk of developing, or treating neuromyelitis optica (NMO) and, more specifically, to methods involving the inhibition of the classical pathway of complement activation.

Abstract: Provided herein are methods for identifying compounds that are inhibitors of a calcium-activated chloride channel. Aminothiophene and aminothiazole compounds, and compositions comprising these compounds, described herein that inhibit efflux of chloride through a calcium-activated chloride channel are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased chloride and fluid secretion, for example, secretory diarrhea.

Abstract: The present disclosure provides pharmaceutical compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The pharmaceutical compositions, pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The pharmaceutical compositions and pharmaceutical preparations may include one or more cyanoquinoline-containing compounds of the embodiments, or an analog or derivative thereof.

Abstract: Provided herein are benzopyrimido-pyrrolo-oxazine-dione (BPO) compounds and pyrimido-pyrrolo-quinoxalinedione (PPQ) compounds, and compositions comprising these compounds, that inhibit cystic fibrosis transmembrane conductance regulator (CFTR) mediated ion transport and that are useful for treating diseases and disorders associated with aberrantly increased CFTR chloride channel activity, such as polycystic kidney disease and secretory diarrheas. The compounds and compositions comprising the compounds described herein may be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

Abstract: Provided herein is a method of treating neuromyelitis optica (NMO) in an animal or human subject comprising administering to the subject a composition comprising a therapeutically effective amount of an Fc region modified anli-AQP4 antibody, thereby treating the NMO in the subject, in some embodiments, the Fc region modified anti-AQP4 antibody is an anti-AQP4 antibody deglycosylated at the amino acid position Asn297. In other embodiments, the Fc region modified anti-AQP4 antibody is an anii-AQP4 antibody F(ab?)2 fragment.

Abstract: Provided herein are small molecule triazolothienopyrimidine compounds that inhibit urea transport activity of solute transporters, particularly the UT-B transporter. The compounds described herein are useful for increasing solute clearance in states of fluid overload and for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.

Abstract: Provided herein are small molecule activators of calcium-activated chloride channels. These small molecules may be used for treatment of diseases and disorders that are treatable by activating calcium-activated chloride channels, such as cystic fibrosis, disorders related to salivary gland dysfunction (for example, Sjogren's syndrome and dysfunction following radiation injury), dry eye syndrome, and intestinal hypomotility.

Abstract: The present disclosure provides pharmaceutical compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The pharmaceutical compositions, pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The pharmaceutical compositions and pharmaceutical preparations may include one or more cyanoquinoline-containing compounds of the embodiments, or an analog or derivative thereof.

Abstract: The present invention is directed to antibodies binding to aquaporin 4 (AQP4) and methods of using such antibodies to treat neuromyelitis optica (NMO) either as a monotherapy or in combination with standard NMO therapies such as immunosuppressives or plasmaphersis.

Abstract: Provided herein are benzopyrimido-pyrrolo-oxazine-dione (BPO) compounds and pyrimido-pyrrolo-quinoxalinedione (PPQ) compounds, and compositions comprising these compounds, that inhibit cystic fibrosis transmembrane conductance regulator (CFTR) mediated ion transport and that are useful for treating diseases and disorders associated with aberrantly increased CFTR chloride channel activity, such as polycystic kidney disease and secretory diarrheas. The compounds and compositions comprising the compounds described herein may be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

Abstract: Provided herein are pyrimido-pyrrolo-quinoxalinedione (PPQ) compounds, and compositions comprising these compounds, that inhibit cystic fibrosis transmembrane conductance regulator (CFTR) mediated ion transport and that are useful for treating diseases and disorders associated with aberrantly increased CFTR chloride channel activity. The compounds, and compositions comprising the compounds, described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, polycystic kidney disease. The compounds may be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

Abstract: Provided herein are bioactive agents comprising a compound that inhibits the ion transport activity of a cystic fibrosis transmembrane conductance regulator (CFTR) and that is linked to a macromolecule that interacts with a cell that expresses CFTR. The bioactive agents described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, secretory diarrhea.

Abstract: Provided herein are methods for identifying compounds that are inhibitors of a calcium-activated chloride channel. Aminothiophene and aminothiazole compounds, and compositions comprising these compounds, described herein that inhibit efflux of chloride through a calcium-activated chloride channel are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased chloride and fluid secretion, for example, secretory diarrhea.

Abstract: Provided herein are small molecule compounds that alter the transport activity of solute transporters, particularly urea transporters. The compounds described herein belong to the phenylsulfoxyoxazole, phenylsulfoxyimidazole, phenylsulfoxythiazole class of compounds. The compounds described herein are useful for increasing solute clearance in states of fluid overload and for treating cardiovascular, renal, and metabolic diseases, disorders, and conditions. Methods for identifying and using these agents that inhibit urea transporters are described herein.

Abstract: The invention provides compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The compositions pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The compositions and pharmaceutical preparations of the invention may comprise one or more bithiazole-containing compounds of the invention, or an analog or derivative thereof.

Abstract: Provided herein are pyrimido-pyrrolo-quinoxalinedione (PPQ) compounds, and compositions comprising these compounds, that inhibit cystic fibrosis transmembrane conductance regulator (CFTR) mediated ion transport and that are useful for treating diseases and disorders associated with aberrantly increased CFTR chloride channel activity. The compounds, and compositions comprising the compounds, described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, polycystic kidney disease. The compounds may be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

Abstract: Disclosed herein are methods of treating diseases including gastrointestinal disorders, such as secretory diarrheas, with the proanthocyanidin oligomer, crofelemer. Also disclosed is the anti-secretory effect of crofelemer on Calcium-activated chloride channels (CaCC) and Cystic fibrosis transmembrane conductance regulator (CFTR).

Abstract: Provided herein are highly water soluble, thiazolidinone derivative compounds and glycine hydrazide derivative compounds that inhibit the ion transport activity of the cystic fibrosis transmembrane conductance regulator (CFTR). The compounds, and compositions comprising the compounds, described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, secretory diarrhea. The compounds may also be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

Abstract: Provided herein are small molecule compounds that alter the transport activity of solute transporters, particularly urea transporters. The compounds described herein belong to the benzenesulfonanilide class of compounds. The compounds described herein are useful for increasing solute clearance in states of fluid overload and for treating cardiovascular, renal, and metabolic diseases, disorders, and conditions. Methods for identifying and using these agents that inhibit urea transporters are described herein.

Abstract: The invention provides compositions, pharmaceutical preparations and methods for inhibition of cystic fibrosis transmembrane conductance regulator protein (CFTR) that are useful for the study and treatment of CFTR-mediated diseases and conditions. The compositions and pharmaceutical preparations of the invention may comprise one or more hydrazide-containing compounds, and may additionally comprise one or more pharmaceutically acceptable carriers, excipients and/or adjuvants. The methods of the invention comprise, in certain embodiments, administering to a patient suffering from a CFTR-mediated disease or condition, an efficacious amount of a hydrazide-containing compound. In other embodiments the invention provides methods of inhibiting CFTR that comprise contacting cells in a subject with an effective amount of a hydrazide-containing compound.