348 results about "Histone deacetylase" patented technology

Improved methods for treatment of cancer are provided. The improvements include the administration of one or more synergistic agents, specifically inhibitors of histone deacetylase proteins and complexes. These synergistic agnets increase the effectiveness of radiation therapy and/or chemotherapies by increasing the sensitivity of tumor cells to treatment.

The present invention provides methods and compositions for inhibiting Hsp90 activity in a cell, comprising contacting the cell with an inhibitor of histone deacetylase 6 (HDAC6)

This invention is directed to a continuous method for measuring the activity of an enzyme that catalyzes the addition of an acetyl group to a residue capable of being acetylated or an enzyme that catalyzes the removal of an acetyl group from an acetylated residue. In particular the present invention is directed to a continuous method for measuring the activity of histone acetyltranferases and histone deacetylase enzymes.

The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can 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 invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be 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. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

The present invention relates to compounds of formula (I):

or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R^2a, R^2b, R^2c, R⁵ and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

The present invention provides FK228 analogs and methods of making and using the same. Such analogs are potent inhibitors of histone deacetylase and, in certain embodiments, are capable of specifically targeting cancerous cells and tissues. In preferred embodiments, these analogs are characterized by a cyclic disulfide design.

Disclosed herein are methods of treating neuroblastomas and medulloblastomas in a subject comprising administering to the subject a phosphatase ligand in an amount effective to treat the subject. Also disclosed herein are method of treating neuroblastomas and medulloblastomas in a subject comprising administering to the subject a histone deacteylase ligand in an amount effective to treat the subject.

The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

Novel acetyloxymethyl esters are disclosed. Methods of treating an illness, including cancer, hemological disorders and inherited metabolic disorders, and treating or ameliorating other conditions using these compounds are also disclosed. The compounds are effective in the inhibition of histone deacetylase.

Disclosed herein are carbonyl compounds of Formula I, II, or III, and others as described herein.

Also disclosed are methods of treating disease, such as cancer, neurological disorders, including polyglutamine-repeat disorders, anemias, thalassemias, inflammatory conditions, autoimmune diseases and cardiovascular conditions, using the compounds of the invention. In addition, methods of modulating the activity of histone deacetylase (HDAC) are also disclosed.

The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth.

The present invention relates to a novel class of hydroxyalkylarylamide derivatives. The instant compounds can be used to treat cancer. The fluorinated arylamide derivatives 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 invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be 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. The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

The invention relates to phthalazinone derivatives and application of the phthalazinone derivatives in the aspect of inhibiting the activity of poly(ADP-ribose)polymerase and the activity of histone deacetylases. The phthalazinone derivatives have the structure of formula (I). The median inhibitory concentration of partial compounds as shown in the formula (I) on the activity of poly(ADP-ribose)polymerase and the activity of histone deacetylases is about 10-7oml.L<-1>. The series of compounds can be used for preventing and treating tumors, local ischemic diseases, diabetes and inflammatory diseases.

The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The invention discloses a hydroxamic acid compound and a preparation method as well as application of the compound. The invention also discloses a medicine combination for restraining the activity of histone deacetylase. The hydroxamic acid compound provided by the invention has good inhibitory effect on the HDAC in vitro, can also enter tumor cells to inhibit the activity of the HDAC in the tumor cells and enhance the expression of acetylated histone and cycle-related proteins and has the anti-tumor effect; and the anti-tumor effect of the hydroxamic acid compound is obviously superior to that of SAHA.

An agent for inhibiting articular cartilage extracellular matrix degradation of the present invention, comprising a histone deacetylase-inhibiting compound as an active ingredient, is effective for the prevention and treatment of diseases and pathological conditions involving the degradation and degeneration of the articular cartilage extracellular matrix, in particular, arthrosteitis, rheumatic arthritis, osteoarthritis, and the like.

Presented herein are methods of generating a multipotent or immature cell from a mature somatic cell, involving contacting a mature somatic cell with one or more small molecule compounds selected from: a histone deacetylase (HDAC) inhibitor; a glycogen synthase kinase 3 (GSK-3) inhibitor; one or more transforming growth factor-beta receptor (TGF-βR) inhibitors; one or more lysine-specific demethylase 1 (LSD1) inhibitors; a cAMP agonist; a histone lysine methyltransferase (EZH2) inhibitor; and a histone methyltransferase (HMTase) G9a inhibitor; valproic acid. Also provided are methods of generating a multipotent or immature cell from a somatic cell, by driving expression of OCT4, or an OCT4 functional homolog or derivative, under the control of a high expressing promoter. Presented herein are also methods of stem cell expansion, stem cell regeneration and differentiation, which comprise contacting stem cells with one or more small chemical compounds.

The present invention provides methods and compositions useful for the elimination of latent HIV reservoirs that persist despite HAART. The methods and compositions overcome this latent barrier by inducing the replication of HIV in latently infected T cells while preventing the spread of the newly produced virions to uninfected cells by providing HAART simultaneously. Compositions of the invention comprise an activator of latent HIV expression, such as prostratin, and an inhibitor of histone deacetylase, such as TSA. A surprising finding of this invention is that the inhibitor of the histone deacetylase synergizes the effect of prostratin thus, allowing administering to a patient a lower, non-toxic dose of prostratin.

The present invention relates to compounds of formula (I):

or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R^2a, R^2b, R^2c, R⁵ and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

The present invention relates to a novel class of substituted nicotinamides. These compounds can 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 invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be 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. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.