Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

The present invention provides methods of preventing and/or reducing risk of neurodegeneration of association cortex, and/or inhibiting or reversing formation of phosphorylated tau or COXIV in the prefrontal cortex of a mammal in need thereof. In certain embodiments, the method comprises administering to the mammal a therapeutically effective amount of an α.sub.2A-adrenergic receptor agonist.

The present invention provides methods of preventing and/or reducing risk of neurodegeneration of association cortex, and/or inhibiting or reversing formation of phosphorylated tau or COXIV in the prefrontal cortex of a mammal in need thereof. In certain embodiments, the method comprises administering to the mammal a therapeutically effective amount of an α.sub.2A-adrenergic receptor agonist.

This invention relates to substituted 4-pyridones of formula 1 ##STR00001##
and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other auto-immune and allergic disorders, allograft rejection, and oncological diseases.

The present disclosure provides pladienolide compounds, pharmaceutical compositions containing such compounds, and pladienolide compounds for use in methods of medical treatment. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are pladienolide compounds for use in methods of treating cancers by administering at least one pladienolide compound disclosed herein and at least one additional therapy

The present disclosure provides pladienolide compounds, pharmaceutical compositions containing such compounds, and pladienolide compounds for use in methods of medical treatment. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are pladienolide compounds for use in methods of treating cancers by administering at least one pladienolide compound disclosed herein and at least one additional therapy

The present invention relates to compositions for facilitating absorption and distribution of α.sub.2-adrenergic agonists, where said composition comprises a substituted benzofuroquinolizine and a α.sub.2-adrenoceptor agonist selected from substituted imidazoles and substituted thiazines and the composition is administered using parenteral extravascular administration to a subject in need of sedation.

The present invention relates to compositions for facilitating absorption and distribution of α.sub.2-adrenergic agonists, where said composition comprises a substituted benzofuroquinolizine and a α.sub.2-adrenoceptor agonist selected from substituted imidazoles and substituted thiazines and the composition is administered using parenteral extravascular administration to a subject in need of sedation.

The present invention relates to compositions for facilitating absorption and distribution of α.sub.2-adrenergic agonists, where said composition comprises a substituted benzofuroquinolizine and a α.sub.2-adrenoceptor agonist selected from substituted imidazoles and substituted thiazines and the composition is administered using parenteral extravascular administration to a subject in need of sedation.

The present invention relates generally to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathy, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to methods for the use of calmodulin inhibitors and calcium channel blockers for treatment of ribosomal disorders and ribosomopathy, e.g. Diamond Blackfan anemia (DBA).