Disclosed herein are novel analogs of cyclosporin, pharmaceutical compositions containing them, and methods for their use in the treatment of dry eye and other conditions.

Disclosed herein are novel analogs of cyclosporin, pharmaceutical compositions containing them, and methods for their use in the treatment of dry eye and other conditions.

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity. In some embodiments, the compounds of the invention re-program the binding of the presenter proteins to protein targets that either do not normally bind to the presenter protein (e.g., do not show detectable binding in mammalian cells absent the compound). In some embodiments, provided compounds re-program presenter protein binding to greatly enhance interaction with a particular target with which it may have some interaction absent the compound. Interactions achieved through such reprogramming result in an ability to modulate the activity of these new targets.

The present disclosure relates to solid state forms of Voclosporin and salts thereof, processes for preparation thereof and pharmaceutical compositions thereof.

Disclosed herein are cyclosporine compounds and methods for use in the treatment or prevention of neutrophil-mediated inflammation, wherein the compounds inhibit the activity of MRP2 and FPR1.

A compound of the Formula (I) is disclosed:

##STR00001##

or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kidney diseases, and hair loss using the same.

The present disclosure relates to solid state forms of Voclosporin and salts thereof, processes for preparation thereof and pharmaceutical compositions thereof.

Disclosed herein are cyclosporine compounds and methods for use in the treatment or prevention of neutrophil-mediated inflammation, wherein the compounds inhibit the activity of MRP2 and FPRL.

The present disclosure provides compositions and methods for producing fungal-derived medicinal compounds in plants. The present disclosure further provides modified plants, seeds, cells, and plant parts comprising intact biosynthetic pathways required for the production of fungal-derived medicinal compounds. Aspects of the disclosure further relate to methods for producing, growing, and breeding modified plants.

The present invention belongs to the technical field of drug synthesis. In particular, the present invention is related to a for preparing a salt of isocyclosporin A, in particular by transesterification of cyclosporin A into a salt of isocyclosporin A.