Methods for specifically inhibiting histone deacetylase-7 and 8
OwnerJeffrey M. Besterman, Zuomei Li +2inventors
InventorsJeffrey M. Besterman, Zuomei Li, Daniel Delorme, Claire Bonfils
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Abstract
This invention relates to the inhibition of histone deacetylase (HDAC) expression and enzymatic activity. The invention provides methods and reagents for inhibiting HDAC-7 and HDAC-8 by inhibiting expression at the nucleic acid level or inhibiting enzymatic activity at the protein level.
Claims50
A method of inhibiting HDAC-7 activity in a cell, comprising contacting the cell with an antisense oligonucleotide complementary to a region of RNA that encodes a portion of HDAC-7, whereby HDAC-7 activity is inhibited.
A method of inhibiting HDAC-7 or HDAC-8 activity in a cell, comprising contacting the cell with a small molecule inhibitor of HDAC-7 selected from the group consisting of:
- N-Hydroxy-4,6-dimethyl-7-[(4-N,N-dimethylaminophenyl)]-2,4-heptadienamide,
- N-(2-Aminophenyl)-3-[4-(4-methylbenzenesulfonylamino)-phenyl]-acrylamide,
- 4-{[4-Amino-6-(2-indanyl-amino)-[1,3,5]-triazin-2-yl-amino]-methyl}-N-(2-amino-phenyl)-benzamide,
- N-(2-Amino-phenyl)-4-(1H-benzimidazol-2-ylsulfanylmethyl)-benzamide,
- N-(2-Aminophenyl)-4-[(3,4-dimethoxyphenylamino)-methyl]-benzamide, and
- N-(2-Amino-phenyl)-4-{[4-(3,4-dimethoxy-phenyl)-pyrimidin-2-ylamino]-methyl}-benzamide.
A method for inhibiting neoplastic cell proliferation in an animal, comprising administering to an animal having at least one neoplastic cell present in its body a therapeutically effective amount of an antisense oligonucleotide complementary to a region of RNA that encodes a portion of HDAC-7 or HDAC-8, whereby neoplastic cell proliferation is inhibited.
A method for inhibiting neoplastic cell proliferation in an animal, comprising administering to an animal having at least one neoplastic cell present in its body a therapeutically effective amount of a small molecule inhibitor of HDAC-7 or HDAC-8
Dependencies are inferred from the claim text.