The invention relates to cyclic compounds of general formula (I): wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification, and their use as pharmaceuticals.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

The present invention relates to a compound of the Formula (I)):

##STR00001##

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

The present invention relates to cyclosporin analogs that are potent inhibitors of cyclophilin D and have low immunosuppressive activity; processes for preparing them; pharmaceutical compositions containing them; and methods for using these analogs and compositions containing them for the treatment of medical conditions, including but not limited to ischemic conditions, such as ischemia-reperfusion (I/R) injury, including myocardial FR injury, cerebral I/R injury, and ocular or retinal I/R injury.

Disclosed herein are autoclavable formulations of cyclosporin A Form 2, methods of making such formulations, and methods of treating diseases of the eye with such formulations.

The present invention relates to cyclosporin analogs that are potent inhibitors of cyclophilin D and have low immunosuppressive activity; processes for preparing them; pharmaceutical compositions containing them; and methods for using these analogs and compositions containing them for the treatment of medical conditions, including but not limited to ischemic conditions, such as ischemia-reperfusion (I/R) injury, including myocardial FR injury, cerebral I/R injury, and ocular or retinal I/R injury.

The present invention relates to a compound of the Formula (I)): ##STR00001##
or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.

The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISA.sub.TX247, and derivatives thereof. Mixtures of ISA.sub.TX247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISA.sub.TX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. The ratio of isomers in a mixture comprises from about 70 to about 80 percent by weight of the E-isomer and from about 20 to about 30 percent by weight of the Z-isomer, based on the total weight of the mixture.

Analogs of cyclosporin-A are disclosed comprising modifications of the substituents as the positions of amino acids 1 and 3, according to the following Formula. The disclosed compounds include compounds having affinity for cyclophilin, including cyclophilin-A, and reduced immunosuppressivity in comparison with cyclosporin-A and analogs thereof modified solely at position 1. ##STR00001##