Disclosed is a method for treating manganese (manganese) toxicity in a subject. The method includes administering to the subject an effective amount of a hypoxia inducible factor (HIF) prolyl hydroxylase inhibitor or a pharmaceutically acceptable salt or solvate thereof.

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds thereof, and use of these compounds in preparing drugs for inhibiting ROCK. ##STR00001##

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds thereof, and use of these compounds in preparing drugs for inhibiting ROCK. ##STR00001##

The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I) ##STR00001##
including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2a, R.sup.2b, R.sup.3, R.sup.3a, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and the subscript n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I) ##STR00001##
including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2a, R.sup.2b, R.sup.3, R.sup.3a, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and the subscript n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

The present invention relates to methods and compositions for the treatment of hemangioma, and particularly, but not exclusively, methods and compositions for the treatment of infantile hemangioma. In certain aspects, the methods comprise locally administering an ACE inhibitor or an ATIIR2 antagonist to a subject. In other aspects, the methods comprise systemically administering two or more of an ACE inhibitor, a beta-blocker and an ATIIR2 antagonist. The present invention also relates to compositions that are suitable for local administration and comprise: an ACEi and a beta-blocker; an ACEi and an ATIIR2 antagonist; a beta-blocker and an AT11R2 antagonist; or, an ACEi, a beta-blocker, and an AT11R2 antagonist.

The present invention relates to methods and compositions for the treatment of hemangioma, and particularly, but not exclusively, methods and compositions for the treatment of infantile hemangioma. In certain aspects, the methods comprise locally administering an ACE inhibitor or an ATIIR2 antagonist to a subject. In other aspects, the methods comprise systemically administering two or more of an ACE inhibitor, a beta-blocker and an ATIIR2 antagonist. The present invention also relates to compositions that are suitable for local administration and comprise: an ACEi and a beta-blocker; an ACEi and an ATIIR2 antagonist; a beta-blocker and an AT11R2 antagonist; or, an ACEi, a beta-blocker, and an AT11R2 antagonist.

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:

##STR00001##

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