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).

The present invention relates to the treatment of cancer. In particular, the invention relates to the therapeutic use of alpha-2 adrenergic receptor agonists for the treatment of cancer. More particularly, apraclonidine, clonidine, guanfacine and guanabenz, which are alpha-2 adrenergic receptor agonists, are all capable of efficiently reducing the growth of solid tumors. The effect is immune-mediated and is abolished in the presence of an alpha-2 antagonist or in mice that are knockout for the alpha-2 adrenergic receptor.

The present invention relates to the treatment of cancer. In particular, the invention relates to the therapeutic use of alpha-2 adrenergic receptor agonists for the treatment of cancer. More particularly, apraclonidine, clonidine, guanfacine and guanabenz, which are alpha-2 adrenergic receptor agonists, are all capable of efficiently reducing the growth of solid tumors. The effect is immune-mediated and is abolished in the presence of an alpha-2 antagonist or in mice that are knockout for the alpha-2 adrenergic receptor.

The present invention provides methods of treating COVID-19 in a subject using methylthioninium compounds.

The present invention provides methods of treating COVID-19 in a subject using methylthioninium compounds.

The invention refers to the use of a sigma ligand, particularly a sigma ligand of formula (I) to prevent and/or treat type-2 diabetes-associated pain and related symptoms. ##STR00001##

The invention relates to compounds of formula I ##STR00001##
wherein is a bond or is absent, V is CH, CR.sup.6 or N; R.sup.0 is H or, if is a bond, may also be alkoxy; R.sup.1 is H or halogen; U is CH or N when is a bond, or, if is absent, U is CH.sub.2, NH or NR.sup.9; R.sup.2 is H, alkylcarbonyl or —CH.sub.2—R.sup.3; R.sup.3 is H, alkyl or hydroxyalkyl; R.sup.4 is H or, if n is not 0 and R.sup.5 is H, may also be OH; R.sup.5 is H, alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, carboxy or alkoxycarbonyl; R.sup.6 is hydroxyalkyl, carboxy, alkoxycarbonyl or —(CH.sub.2).sub.q—NR.sup.7R.sup.8, q being 1, 2 or 3 and each of R.sup.7 and R.sup.8 independently being H or alkyl or R.sup.7 and R.sup.8 forming with the N atom bearing them a ring; R.sup.9 is alkyl or hydroxyalkyl; A is —(CH.sub.2).sub.p—, —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—; G is substituted phenyl or G.sup.1 or G.sup.2 ##STR00002##
wherein Q is O or S and X is CH or N; and Y.sup.1, Y.sup.2 and Y.sup.3 may each be CH or N; and n is 0 when A is —CH.sub.2CH.sub.2CH(OH)— or —COCH.sub.2CH(OH)—, and n is 0, 1 or 2 when A is —(CH.sub.2).sub.p—, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; and to salts thereof.

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDMIA, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDMIA, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.