Histone deacetylases, and uses related thereto
AssigneePresident and Fellows of Harvard College
InventorsSTUART L. SCHREIBER, JACK TAUNTON, CHRISTIAN A. HASSIG, TIMOTHY F. JAMISON
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Abstract
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.
Claims12
1-48. (canceled)
A method for modulating one or more of growth, differentiation, or survival of a mammalian cell responsive to HDx-mediated histone deacetylation, comprising treating the cell with an effective amount of an agent which modulates the deacetylase activity of an HDx polypeptide thereby altering, relative to the cell in the absence of the agent, at least one of (i) rate of growth, (ii) differentiation, or (iii) survival of the cell.
50-73. (canceled)
A composition for inhibiting a histone deacetylase comprising a compound represented by the general formula A-B-C, wherein
- A is selected from the group consisting of cycloalkyls, unsubstituted and substituted aryls, heterocyclyls, amino acyls, and cyclopeptides;
- B is selected from the group consisting of substituted and unsubstituted C4-C8 alkylidenes, C4-C8 alkenylidenes, C4-C8 alkynylidenes, and -(D-E-F)-, in which D and F are, independently, absent or represent a C2-C7 alkylidene, a C2-C7 alkenylidene or a C2-C7 alkynylidene, and E represents O, S, or NR′, in which R′ represents H, a lower alkyl, a lower alkenyl, a lower alkynyl, an aralkyl, aryl, or a heterocyclyl;
- and
- C is selected from the group consisting of
- and a boronic acid;
- in which Z represents O, S, or NR5, and Y;
- R5 represents a hydrogen, an alkyl, an alkoxycarbonyl, an aryloxycarbonyl, an alkylsulfonyl, an arylsulfonyl or an aryl;
- R′6 represents hydrogen, an alkyl, an alkenyl, an alkynyl or an aryl;
- and R7 represents a hydrogen, an alkyl, an aryl, an alkoxy, an aryloxy, an amino, a hydroxylamino, an alkoxylamino or a halogen;
- with the proviso that the compound is not trapoxin.
A composition for inhibiting a histone deacetylase comprising a compound represented by the general formula A-B-C, wherein
- A is selected from the group consisting of cycloalkyls, unsubstituted and substituted aryls, heterocyclyls, amino acyls, and cyclopeptides;
- B is selected from the group consisting of substituted and unsubstituted C4-C8 alkylidenes, C4-C8 alkenylidenes, C4-C8 alkynylidenes, and -(D-E-F)-, in which D and F are, independently, absent or represent C2-C7 alkylidenes, C2-C7 alkenylidenes or C2-C7 alkynylidenes, and E represents O, S, or NR′, in which R′ represents H, a lower alkyl, a lower alkenyl, a lower alkynyl, an aralkyl, an aryl, or a heterocyclyl;
- and
- C is selected from the group consisting of
- in which R9 represents a hydrogen, an alkyl, an aryl, a hydroxyl, an alkoxy, an aryloxy or an amino,
- with the proviso that the inhibitor compound is not trichostatin.
A composition for inhibiting a histone deacetylase comprising a compound represented by the general formula A-B-C, wherein
- A is selected from the group consisting of cycloalkyls, unsubstituted and substituted aryls, heterocyclyls, amino acyls, and cyclopeptides;
- B is selected from the group consisting of substituted and unsubstituted C4-Ca alkylidenes, C4-C8 alkenylidenes, C4-C8 alkynylidenes, and -(D-E-F)-, in which D and F are, independently, absent or represent a C2-C7 alkylidene, a C2-C7 alkenylidene, or a C2-C7 alkynylidenes, and E represents O, S, or NR′, in which R′ is H, lower alkyl, lower alkenyl, lower alkynyl, aralkyl, aryl, or heterocyclyl;
- and
- C represents
- in which Y is O or S, and R7 represents a hydrogen, an alkyl, an aryl, an alkoxy, an aryloxy, an amino, a hydroxylamino, an alkoxylamino, or a halogen.
Dependencies are inferred from the claim text.