Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

A morphinan derivative represented by the following general formula (I):

##STR00001##

wherein R.sup.1 represents hydrogen, C.sub.1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms, and the alkylene moiety has 1 to 5 carbon atoms, etc.; R.sup.2 represents heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S and at least one carbon atom as ring-constituting atoms, containing at least one set of adjacent ring-constituting atoms bound by a double bond, and further substituted with at least one oxo group; Y binds to a carbon atom as a ring-constituting atom of R.sup.2; R.sup.3, R.sup.4, and R.sup.5 represent hydrogen, hydroxy, etc.; R.sup.6a and R.sup.6b represent hydrogen, etc.; R.sup.7 and R.sup.8 represent hydrogen, etc.; R.sup.9 and R.sup.10, which are the same or different, represent hydrogen, etc.; X represents O or CH.sub.2; and Y represents C(═O)); a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic drug, antidepressant, etc.

The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Provided herein are methods of reducing the incident of disease flares in a subject in need thereof.

Provided herein are methods of reducing the incident of disease flares in a subject in need thereof.

Provided herein are methods of improving kidney function in a subject in need thereof.

Provided herein are methods of improving kidney function in a subject in need thereof.

Provided herein are methods of improving kidney function in a subject in need thereof.

Provided herein are methods of improving kidney function in a subject in need thereof.

An amorphous solid form of a compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and sodium cations is provided. This is compound is useful for the treatment of hypertension and/or heart failure.