319 results about "HDAC inhibitor" patented technology

The present invention relates to quinazoline containing zinc-binding moiety based derivatives that have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

Disclosed herein are methods and low dose regimens for increasing fetal hemoglobin levels in patients with red blood cell disorders, such as beta thalassemia, sickle cell disease, other anemias, or blood loss. Fetal and total hemoglobin levels and red blood cell counts are increased by administering 2,2-dimethylbutyrate (DMB) alone or in combination with hydroxyurea, decitabine or an HDAC inhibitor. Treatment can be continued for at least two weeks.

The invention relates to a pharmaceutical composition and oral dosage forms comprising an HDAC inhibitor in combination with an enhancer to promote absorption of the HDAC inhibitor at the GIT cell lining. The enhancer is a medium chain fatty acid or a medium chain fatty acid derivative having a carbon chain length of from 6 to 20 carbon atoms. Preferably, the solid oral dosage form is a controlled release dosage form such as a delayed release dosage form.

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula:

wherein: A is an aryl group; Q¹ is a covalent bond or an aryl leader group; J is an amide linkage selected from: —NR¹C(═O)— and —C(═O)NR¹—; R¹ is an amido substituent; X is an ether heteroatom, and is —O— or —S—; and, R² and R³ are each independently an ether group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q¹ is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O)₂NR¹— and —NR¹S(═O)₂—; R¹ is a sulfonamido substituent; and, Q² is an acid leader group; with the proviso that if J is —S(═O)₂NR¹—, then Q¹ is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

The present invention relates to HSP90 inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.

The present invention relates to methods of treating cancers, e.g., mesothelioma or lymphoma. More specifically, the present invention relates to methods of treating mesothelioma or diffuse large B-cell lymphoma (DLBCL), by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

The present invention relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with HDAC6, having a Formula I:

where R, L, X¹, X², X³, X⁴, Y¹, Y², Y³, and Y⁴ are described herein.

The present invention relates to VEGFR inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.

The present invention relates to methods of treating cancers, e.g., lymphoma. More specifically, the present invention relates to methods of treating diffuse large B-cell lymphoma (DLBCL), by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

Provided herein are combinations that include an HDACi and a PD-1 inhibitor that are useful for treating cancer, including reducing and/or preventing cancer metastasis. The combination is also useful for treating cancer that has been previously treated with a PD-L1 inhibitor.

A method of ameliorating or abrogating the effects of a neurodegenerative disorder, such as amyotrophic lateral sclerosis (ALS), includes administering a histone deacetylase (HDAC) inhibitor in a subject in need thereof. The HDAC inhibitor includes sodium butyrate or sodium phenylbutyrate.

The present invention provides pharmaceutical compositions of an HDAC inhibitor and a chelatable metal compound. In one embodiment, the invention provides a method of treating cancer and alleviating the side effects of the HDAC inhibitor by administering the pharmaceutical composition. In another embodiment, the present invention also provides pharmaceutical compositions of metal HDAC inhibitor chelate complexes. In another embodiment, the invention provides methods of treating cancer by administering the pharmaceutical compositions. The invention provides crystalline compositions of metal HDAC inhibitor chelate complexes and methods of producing same.

The invention relates to combinations comprising an HDAC inhibitor and a Her2 inhibitor for the treatrent of breast cancer in a subject in need thereof. The invention also relates to combinations comprising an HDAC inhibitor and a PI3K inhibitor for the treatment of breast cancer in a subject in need thereof. Also provided herein are methods for treating breast cancer in a subject in need thereof comprising administering to the subject an effective amount of one of the above combinations. Further provided are methods for inhibiting migration and/or invasion of a breast cancer cell in a subject by administering to the subject a HDAC6 specific inhibitor.

This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula:

wherein: Cy is independently a cyclyl group; Q¹ is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J¹ is independently a covalent bond or —C(═;O)—; J² is independently —C(═O)— or —S(═O)₂—; Q₂ is independently an acid leader group; wherein: Cy is independently: C_3-20carbocyclyl, C_3-20heterocyclyl, or C_5-20aryl; and is optionally substituted; Q¹ is independently: a covalent bond; C_1-7alkylene; or C_1-7alkylene-X—C_1-7alkylene, —X—C^1-7alkylene, or C_1-7alkylene-X—, wherein X is —O— or —S—; and is optionally substituted; Q² is independently: C_4-8alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q² is independently: C_5-20arylene; C_5-20arylene-C_1-7alkylene; C_1-7alkylene-C_5-20arylene; or, C_1-7alkylene-C_5-20arylene-C_1-7alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.