Abstract: This invention provides a compound having the structure: wherein R1 is H, halogen, —NR5R6, —NR5—C(?0)-R6, —NH—C(?O)—OR7, —OR7, —NO2, —CN, —SR7, —SO2R7, —CO2R7, CF3, —SOR7, —POR7, —C(?S)R7, —C(?O)—NR5R6, —CH2—C(?O)—NR5R6, —C(?NR5)R6, —P(?O)(OR5)(OR6), —P(OR5)(OR6), —C(?S)R7, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R5, R6, and R7 and are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(?O)OR8, C(?O)R8, —C(?O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R8, R9 and R10 are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is aryl or heteroaryl; and each occurrence of Z is independently present or

Abstract: This invention provides methods for treating a subject afflicted with cancer, comprising concurrently administering (i) an HDAC 6-selective inhibitor and (ii) a suitable cytotoxic agent such as SAHA, doxorubicin or etoposide. This invention also provides methods for inducing the death of a transformed cell such as a cancer cell, comprising concurrently contacting the cell with (i) an HDAC 6-selective inhibitor and (ii) a suitable cytotoxic agent such as SAHA, doxorubicin or etoposide.

Abstract: This invention provides a compound having the structure: wherein R1 is H, halogen, —NR5R6, —NR5—C(?O)—R6, —NH—C(?O)—OR7, —OR7, —NO2, —CN, —SR7, —SO2R7, —CO2R7, CF3, —SOR7, —POR7, —C(?S)R7, —C(?O)—NR5R6, —CH2—C(?O)—NR5R6, —C(?NR5)R6, —P(?O)(OR5)(OR6), —P(OR5)(OR6), —C(?S)R7, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R5, R6, and R7 and are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(?O)OR8, C(?O)R8, —C(?O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R8, R9 and R10 are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is aryl or heteroaryl; and each occurrence of Z is independently present or

Abstract: This invention provides a compound having the structure: wherein R1 is H, halogen, —NR5R6, —NR5—C(?O)—R6, —NH—C(?O)—OR7, —OR7, —NO2, —CN, —SR7, —SO2R7, —CO2R7, CF3, —SOR7, —POR7, —C(?S)R7, —C(?O)—NR5R6, —CH2—C(?O)—NR5R6, —C(?NR5)R6, —P(?O)(OR5)(OR6), —P(OR5)(OR6), —C(?S)R7, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R5, R6, and R7 and are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R2 and R3 are each, independently, H, halogen, —NH2, —CX3, —C(?O)OR8, C(?O)R8, —C(?O)NR9R10, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R8, R9 and R10 are each, independently, H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar1—Z— or —Z—Ar1—Z—, wherein Ar1 is aryl or heteroaryl; and each occurrence of Z is independently present or

Abstract: This disclosure is related to compounds having the structure wherein Ar1, Ar2, R1-R6, Z, m, n, o, and p are defined herein. This disclosure also relates to pharmaceutical compositions comprising the above compounds and methods for their use.

Abstract: This invention provides methods for treating a subject afflicted with cancer, comprising concurrently administering (i) an HDAC 6-selective inhibitor and (ii) a suitable cytotoxic agent such as SAHA, doxorubicin or etoposide. This invention also provides methods for inducing the death of a transformed cell such as a cancer cell, comprising concurrently contacting the cell with (i) an HDAC 6-selective inhibitor and (ii) a suitable cytotoxic agent such as SAHA, doxorubicin or etoposide.

Abstract: The present application is directed to a method of treating diseases of the central nervous system (CNS) comprising administering to a individual in need of treatment a therapeutically effective amount of an inhibitor of histone deacetylase. In particular embodiments, the CNS disease is a neurodegenerative disease. In further embodiments, the neurogenerative disease is an inherited neurodegenerative disease, such as those inherited neurodegenerative diseases which are polyglutamine expansion diseases. The individual can be a mammal such as a primate or human.

Abstract: The present application is directed to a method of treating diseases of the central nervous system (CNS) comprising administering to a individual in need of treatment a therapeutically effective amount of an inhibitor of histone deacetylase. In particular embodiments, the CNS disease is a neurodegenerative disease. In further embodiments, the neurogenerative disease is an inherited neurodegenerative disease, such as those inherited neurodegenerative diseases which are polyglutamine expansion diseases. The individual can be a mammal such as a primate or human.

Abstract: The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or hydrate thereof, in a first treatment procedure, and a second amount of an anti-cancer agent in a second treatment procedure. The first and second amounts together comprise a therapeutically effective amount. The effect of the HDAC inhibitor and the anti-cancer agent may be additive or synergistic.

Abstract: The present invention features, inter alia, purified antibodies that selectively bind an isolated or recombinant histone deacetylase polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 2, which comprises a histone deacetylase catalytic domain at amino acids 635 to 953 of SEQ ID NO: 2, purified antibodies that selectively bind a biologically active fragment of the polypeptide of SEQ ID NO: 2, which fragment exhibits histone deacetylase activity, transcription repression activity, and the ability to deacetylate cellular substrates, purified antibodies that selectively bind an isolated or recombinant histone deacetylase polypeptide encoded by a nucleotide sequence as set forth in SEQ ID NO: 1, purified antibodies that selectively bind an isolated or recombinant histone deacetylase polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 2 lacking a nuclear localization signal, and purified antibodies that selectively bind an isolated or recombinant histone deacetylase polyp

Abstract: The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: The present invention relates to a method for the treatment of cancer in a patient in need thereof. The method comprises administering to a patient in need thereof a first amount of a histone deacetylase inhibitor in a first treatment procedure, and a second amount or dose of radiation in a second treatment procedure. The first and second treatments together comprise a therapeutically effective amount. The combination of the HDAC inhibitor and radiation therapy is therapeutically synergistic.

Abstract: The present invention features substantially pure HDAC9, HDAC9a, HDAC9(?NLS), HDAC9a(?NLS), an HDRP(?NLS) polypeptides, and isolated nucleic acid molecules encoding those polypeptides. The present invention also features vectors containing HDAC9, HDAC9a, HDAC9(?NLS), HDAC9a(?NLS), and HDRP(?NLS) nucleic acid sequences, and cells containing those vectors.

Abstract: The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

Abstract: The present invention features substantially pure HDAC9, HDAC9a, HDAC9(?NLS), HDAC9a(?NLS), an HDRP(?NLS) polypeptides, and isolated nucleic acid molecules encoding those polypeptides. The present invention also features vectors containing HDAC9, HDAC9a, HDAC9(?NLS), HDAC9a(?NLS), and HDRP(?NLS) nucleic acid sequences, and cells containing those vectors.

Abstract: The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

Abstract: The present invention provides three-dimensional structural information from the hyperthermophilic bacterium Aquifex aeolicus which is a histone deacetylase-like protein (HDLP). HDLP shares 35.2% amino acid sequence identity with human histone deacetylase (HDAC1). The present invention further provides three-dimensional structural information of HDLP bound by inhibitor molecules. The three-dimensional structural information of the present invention is useful to design, isolate and screen deacetylase inhibitor compounds capable of inhibiting HDLP, HDAC family members and HDLP-related molecules. The invention also relates to nucleic acids encoding a mutant HDLP which facilitates the determination of the three-dimensional structure of HDLP in the presence of a zinc atom.

Abstract: The present invention features substantially pure HDAC9, HDAC9a, HDAC9(?NLS), HDAC9a(?NLS), an HDRP(?NLS) polypeptides, and isolated nucleic acid molecules encoding those polypeptides. The present invention also features vectors containing HDAC9, HDAC9a, HDAC9(?NLS), HDAC9a(?NLS), and HDRP(?NLS) nucleic acid sequences, and cells containing those vectors.

Abstract: The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.