Provided herein are compounds and their pharmaceutically acceptable salts, lipid particles comprising such compounds or pharmaceutically acceptable salts thereof and compositions of the foregoing that can be used to reduce immune intolerance in a subject, for example, to treat autoimmune disorders, or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy. The compounds have the following structural formula:

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wherein values for the variables (e.g., Ring A, L, R.sup.1, R.sup.2, R.sup.3, m) are as described herein.

A compound of formula (1a), (1b) or (1c) wherein: n is 1 or 2; R.sup.N is H or Me; R.sup.1 is optionally one or more halo or methyl groups; R.sup.2a and R.sup.2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH.sub.2OH; R.sup.2c and R.sup.2d (if present) are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH.sub.2OH; R.sup.3a and R.sup.3b are independently selected from H and Me; R.sup.4a is selected from OH, NH.sub.2, C(O)NH.sub.2, and CH.sub.2OH; R.sup.4b is either H or Me; R.sup.5 is either H or Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C.sub.5-12 heteroaryl. ##STR00001##

Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX). ##STR00001##

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

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Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

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Described herein is the bromodomain inhibitor 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, including crystalline forms, amorphous forms, solvates, and hydrates thereof, as well as pharmaceutical compositions that include this bromodomain inhibitor. In some embodiments, the pharmaceutical composition comprises 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one that has been processed by micronization or spray dried dispersion. In some embodiments, the pharmaceutical composition further comprises at least one polymer. In some embodiments, the pharmaceutical composition comprises a solid polymer matrix comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one and at least one polymer. Pharmaceutical compositions comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one are useful for the treatment of cancer or neoplastic disease.

Described herein is the bromodomain inhibitor 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, including crystalline forms, amorphous forms, solvates, and hydrates thereof, as well as pharmaceutical compositions that include this bromodomain inhibitor. In some embodiments, the pharmaceutical composition comprises 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one that has been processed by micronization or spray dried dispersion. In some embodiments, the pharmaceutical composition further comprises at least one polymer. In some embodiments, the pharmaceutical composition comprises a solid polymer matrix comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one and at least one polymer. Pharmaceutical compositions comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one are useful for the treatment of cancer or neoplastic disease.

Bicyclic compounds for decreasing the expression of bacterial virulence factors thereby preventing, mitigating, or treating bacterial infection are provided.

Bicyclic compounds for decreasing the expression of bacterial virulence factors thereby preventing, mitigating, or treating bacterial infection are provided.

The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (DGAT2) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardio-renal diseases such as chronic kidney diseases and heart failure and related diseases and conditions. ##STR00001##