This invention relates to the methylation of histones, in particular to a previously uncharacterised group of histone H3 methylases which comprise a SET domain and which methylate either lysine 4 within the amino tail of histone H3 or within the histone H3 core. Methylation by these methylases, in particular trimethylation, is shown to be important for transcriptional activity.

Compounds that may be used to inhibit histone deacetylase having the formula Z-Q-L-M or Z-L-M wherein M is a substituent capable of complexing with a deacetylase catalytic site and/or a metal ion; L is a substituent providing between 0 10 atoms separation between the M substituent and the remainder of the compound; and Z and Q are as defined herein.

Histone deacetylase inhibitors and uses thereof are provided that have the general formula ##STR00001## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each independently selected from the group consisting of hydrogen, a substituted or unsubstituted straight chained C.sub.1-12 alkyl, C.sub.2-12 aminoalkyl or C.sub.2-12 oxaalkyl, and a substituted and unsubstituted 3, 4, 5, 6, 7 or 8 membered ring, with the proviso that R.sub.3 and R.sub.4 are not both hydrogen; R.sub.5 is selected from the gro...

The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

Disclosed are compounds which inhibit histone deacetylase (HDAC) enzymatic activity. Also disclosed are pharmaceutical compositions comprising such compounds as well as methods to treat conditions, particularly proliferative conditions, mediated at least in part by HDAC.

Histone deacetylase inhibitors and uses thereof are provided that have the general formula ##STR00001## whereinR.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each independently selected from the group consisting of hydrogen, a substituted or unsubstituted straight chained C.sub.1-12 alkyl, C.sub.2-12 aminoalkyl or C.sub.2-12 oxaalkyl, and a substituted and unsubstituted 3, 4, 5, 6, 7 or 8 membered ring, with the proviso that R.sub.3 and R.sub.4 are not both hydrogen;R.sub.5 is selected from the group...

Compounds that may be used to inhibit histone deacetylase having the formula Z-Q-L-M or Z-L-M wherein M is a substituent capable of complexing with a deacetylase catalytic site and/or a metal ion; L is a substituent providing between 0-10 atoms separation between the M substituent and the remainder of the compound; and Z and Q are as defined herein.

Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic r...

Compounds that may be used to inhibit histone deacetylase having the formula Z-Q-L-M or Z-L-M wherein M is a substituent capable of complexing with a deacetylase catalytic site and/or a metal ion; L is a substituent providing between 0-10 atoms separation between the M substituent and the remainder of the compound; and Z and Q are as defined herein.