A method of enhancing p53 activity of a p53 mutant polypeptide is provided. The method includes interacting a compound to an open L1/S3 binding site of the p53 mutant polypeptide, where the p53 activity of the p53 mutant polypeptide is enhanced in the presence of the compound. Compounds were identified from databases of compounds for virtual drug screening. Methods of screening for compounds that enhance p53 activity by binding to the open L1/S3 binding site, and methods of treatment using the identified compounds, are also provided.

A method of enhancing p53 activity of a p53 mutant polypeptide is provided. The method includes interacting a compound to an open L1/S3 binding site of the p53 mutant polypeptide, where the p53 activity of the p53 mutant polypeptide is enhanced in the presence of the compound. Compounds were identified from databases of compounds for virtual drug screening. Methods of screening for compounds that enhance p53 activity by binding to the open L1/S3 binding site, and methods of treatment using the identified compounds, are also provided.

Therapeutic combinations of hepatitis B virus (HBV) vaccines and a capsid assembly modulator are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the disclosed therapeutic combinations are also described.

Therapeutic combinations of hepatitis B virus (HBV) vaccines and a capsid assembly modulator are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the disclosed therapeutic combinations are also described.

The invention provides compounds of formula (I) with substituents as specified in claim 1 for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceuticals compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to over-expression of O-GlcNAcase or accumulation of O-GlcNac. ##STR00001##

The present invention relates to novel compounds of Formula (I), wherein M, A and Y are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR.sub.4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR.sub.4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR.sub.4 is involved. ##STR00001##

The present invention relates to novel compounds of Formula (I), wherein M, A and Y are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR.sub.4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR.sub.4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR.sub.4 is involved. ##STR00001##

The present invention relates to novel compounds of Formula (I), wherein M, A and Y are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR.sub.4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR.sub.4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR.sub.4 is involved. ##STR00001##

Described herein are IRE1α inhibitors, compositions containing such inhibitors, and methods of treatment that include administration of such compounds. Exemplary compounds are provided throughout the application.

The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.