The present invention relates to SHIP inhibitor compounds and methods for using these compounds. In particular, the present invention discloses the following methods: (i) a method of treating graft versus host disease in a subject; (ii) a method of inhibiting a SHIP1 protein in a cell; (iii) a method of selectively inhibiting a SHIP1 protein in a cell; (iv) a method for treating or preventing graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant; (v) a method of modulating SHIP activity in a cell expressing SHIP1 or SHIP2; (vi) a method of ex vivo or in vitro treatment of transplants; (vii) a method of inhibiting tumor growth and metastasis in a subject; (viii) a method of treating a hematologic malignancy in a subject; (ix) a method of inducing apoptosis of multiple myeloma cells; (x) a method of treating multiple myeloma in a subject; (xi) a method of inhibiting the proliferation of a human breast cancer cell; and (xii) a method of treating breast cancer in a subject.

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described.

Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

The present application provides a compound of formula I:

##STR00001##

or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, wherein R.sup.1-R.sup.10, m, n, p, and are as described herein. The present invention relates generally to FXR modulators and to methods of making and using said compounds.

The present invention provides compounds of Formula I,

##STR00001##

pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.

The invention relates to compounds of general formula (I):

##STR00001##

wherein R.sup.2a, R.sup.2b, R.sup.3a, R.sup.3b, R.sup.5, Y and R.sup.7 are as defined herein are selective agonists at the FXR receptor and are useful for the treatment or prevention of diseases and conditions including nonalcoholic steatohepatitis (NASH); primary biliary cirrhosis; primary sclerosing cholangitis; biliary atresia; cholestatic liver disease; hepatitis C infection; alcoholic liver disease; fibrosis; and liver damage arising from fibrosis.

A transfection reagent composition comprising: 30-60 MOL % of an cationic lipid, or pharmaceutical acceptable salt thereof; 10-60 MOL % structural lipid; a sterol and 0.1 to about 10 MOL % of a stabilizing agent is provided. The reagent is particularly adapted for neuron and related cell types. A method of manufacturing LNP including nucleic acid for selective uptake into either neurons or astrocytes or neural progenitor cells is also provided.

Disclosed are compounds of formula (I), wherein X, Y, Z are annular atoms comprised in a five-membered carbocyclic or heterocyclic ring, selected from the group consisting of CH, NH, N, O, S; said carbocyclic or heterocyclic ring being optionally substituted with amino (C.sub.1-C.sub.4) linear or branched alkyl or guanidine or guanidino (C.sub.1-C.sub.4) linear or branched alkyl; with the proviso that the heterocycle ring is not furyl; n is 0 or 1; R is H or OH; the dotted line represents an optional double bond C═C; the thick line represents a bond in the β configuration; the wavy line represents a bond both in the α and β configuration; their enantiomeric and/or diastereomeric mixtures, their pharmaceutically acceptable salts, their solvates, hydrates; their metabolite and metabolic precursors. The compounds of formula (I) are for use as medicaments, in particular for the treatment of acute or chronic heart failure. Oral administration is also possible.

##STR00001##

The invention relates to the compounds or its pharmaceutical acceptable polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II, formula III, formula IV, formula V, formula VI, formula VII, formula VIII, formula IX, formula X, formula XI formula XII, formula XIII, formula XIV, formula XV, formula XVI, or formula XVII and the methods for the treatment of eye diseases may be formulated for topical eye drop, topical paste, ocular solution, device-drug delivery, oral, buccal, rectal, topical, transdermal, transmucosal, lozenge, spray, intravenous, oral solution, nasal spray, oral solution, suspension, oral spray, buccal mucosal layer tablet, parenteral administration, syrup, or injection. Such compositions may be used to treatment of glaucoma, presbyopia, IOP, cataract, dry eye and oGVHD.

Provided are panaxdiol-type ginsenoside derivatives having structures as shown in formula I or formula II. Also provided are the uses thereof in the preparation of drugs for preventing and treating atherosclerosis. The panaxdiol-type ginsenoside derivatives have low cytotoxicities, can significantly reduce the percentages of the areas of atherosclerotic plaques in apoE−/− mice, can also effectively reduce the levels of low-density lipoprotein cholesterol and increase the levels of high-density lipoprotein cholesterol in serums of mice, and can significantly reduce the local TNF-α levels in the arteries of apoE−/− mice and have good anti-inflammatory effects; at a dose of 30 μM, the panaxdiol-type ginsenoside derivatives can significantly reduce the degrees of the formation of RAW264.7 cell-derived foam cells. In addition, the preparation methods for the panaxdiol-type ginsenoside derivatives are easy to operate and obtain high yields.