Provided herein in part is a compound of Formula (I): or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of Formula I, and methods of using the compounds, e.g, in the treatment of CNS-related disorders.

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The present invention provides compounds represented by Formula I, or pharmaceutically acceptable salts, prodrugs and esters thereof,

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The invention also provides pharmaceutical compositions comprising these compounds and methods of using this compounds for treating FXR-mediated or TGR5-mediated diseases or conditions.

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.

Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. These compounds are conjugates of glucocorticoids with rho-kinase inhibitors. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.19, R.sup.5, R.sup.3a, R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, R.sup.4a, R.sup.4b, R.sup.6a, R.sup.6b, R.sup.7a, R.sup.7b, R.sup.11a, R.sup.11b, R.sup.12a, R.sup.12b, R.sup.18, R.sup.D, and q are defined herein. L is selected from the group consisting of: wherein A indicates the point of attachment at C17 and wherein X is selected from the group consisting of C(0)N(R.sup.55a)(R.sup.55b), N(R.sup.55a)(R.sup.55b), N(R.sup.55b)C(O)(R.sup.55a), and R.sup.55C wherein R.sup.55c is carbon-bound substituted or unsubstituted heteroaryl or substituted or unsubstituted aryl. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

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The present invention relates to the development of the cationic progesterone compounds as a novel anti-tumor agent. The present invention provides a method for the preparation of novel series of progesterone derivatives. The invention also provides information related to highly selective anti-cancer activities of these compounds in wide range of cancer cell irrespective of their progesterone receptor status. Thus, the presently disclosed cationic progesterone compounds offer a viable option as anti-cancer therapeutics.

A novel delivery system for drugs, and especially macromolecules such as proteins or oligonucleotides through biological membranes is provided, and specifically delivery of siRNA. The delivery system comprises conjugation of the macromolecule drug to a moiety that enables effective passage through the membranes. Respectively, novel compounds and pharmaceutical compositions are provided, utilizing said delivery system. In one aspect of the invention, the compounds may be utilized in medical practice, for example, in delivery of siRNA or antisense oligonucleotides across biological membranes for the treatment of medical disorders.

Described herein protein steroid conjugates that are useful, for example, for the target-specific delivery of glucocorticoids (GCs) to cells.

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 invention relates to diagnostic, detection, screening and imaging methods. In various embodiments, methods of diagnosis, detection, screening and imaging include administering a cationic steroid antimicrobial or CSA to a subject having or at risk of having an infection or a hyperproliferative disorder (e.g., a tumor, cancer or neoplasia) in an amount effective to diagnose or detect the infection or the hyperproliferative disorder (e.g., a tumor, cancer or neoplasia) in the subject. In a particular aspect, a detectable CSA, namely CSA-13 labeled with .sup.99mTc is used to detect the presence of an infection.