96 results about "HDAC6" patented technology

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

Disclosed are a dual regulator for mGluR5 and HDAC6 and use thereof. More specifically, disclosed are a compound that simultaneously regulates mGluR5 and HDAC6, and use thereof as a therapeutic agent for movement disorders.

The invention belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical composition of an HDAC6 inhibitor and a BTK inhibitor and application of the pharmaceutical composition. According to the present invention, the BTK inhibitor and the HDAC6 inhibitor are combined for use to provide the synergistic effect, such that the tumor inhibition effect is significantly enhanced, the medication dosage and the medication period can be improved, the side effect of the drug can be easily reduced, and the compliance of the patient on the drug can be easily improved.

Myotonic Dystrophy type 1 (DM1) is an inherited disease characterized by multi-systemic symptoms, particularly in skeletal muscles (progressive weakness and atrophy, myotonia). The inventors screened 7 500 bioactive compounds for their ability to improve the myogenic fusion and reduce the molecular hallmarks of DM1 skeletal muscle cells. The inventors found that five compounds, all inhibiting HDAC6, a cytoplasmic histone deacetylase, were effective at the micromolar range in normalizing the myogenic fusion, reducing the number of nuclear foci of mutant DMPK mRNA, decreasing the expression level of DMPK mRNA, restoring the splicing of several genes, and increasing the acetylation of SMAD3, a transcription factor involved in muscle development. The effects of HDAC6 inhibitors were observed both in immortalized and hiPSC-derived skeletal muscle cells from DM1 patients, and in different stages of differentiation. Thus, the present invention relates to the use of selective HDAC6 inhibitors for the treatment of DM1.

The present invention discloses a coumarin HDAC6 inhibitor and its preparation method and application, belonging to the field of chemical medicine technology. The present invention provides coumarin compounds shown in Formula I, Formula II and Formula III. Based on the structure of coumarin, the characteristic group of HDAC6 inhibitor hydroxamic acid is introduced to achieve good homologous selectivity for HDAC1 / 6; at the enzyme level, cell level and animal experiment level, it is verified that the compound has excellent target inhibition effect; by studying the example of HDAC6-NF-κB participating in the inflammatory response of colonic tissue, a new practical basis is provided for the treatment of ulcerative colitis. The compound provided by the present invention can be used as a new HDAC6 inhibitor to prevent and treat HDAC6-related diseases, especially it is expected to solve the shortcomings of some current small molecule drugs for the treatment of ulcerative colitis, such as poor relief effect and large side effects.

Formulations of HDAC6 inhibitors that traverse the blood brain barrier in the hypothalamus and inhibit HDAC6 in arcuate AgRP neurons in the hypothalamus are effective for causing weight loss in obese individuals. These inhibitors also restore leptin sensitivity in leptin resistant individuals.

A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, for use in a method of prevention, treatment or amelioration of an HDAC6-mediated disease, wherein: A represents a cycloalkyl ring or a single bond and wherein A is optionally substituted; X1 and X2 each independently represent a group selected from O, S, NR2 and CR2R2, X3 represents N or CR2, Y represents (CR2R2)m, R1 represents an E3 ligase ligand; each R2 independently represents a group selected from 10 H and C1 to C12 hydrocarbon group that is optionally substituted; L represents a linker group; m represents an integer from 1 to 6; and n represents an integer from 0 to 3.

The present invention provides histone deacetylase 6 (HDAC6) inhibitors. The compounds provided in the present invention may be useful for methods of treating or preventing diseases or conditions associated with HDAC6.

Formulations of HDAC6 inhibitors passing through the blood brain barrier in hypothalamus and inhibiting HDAC6 in the arctuate AgRP neurons in the hypothalamus, are effective to cause weight loss in obese individuals. These inhibitors also restore leptin sensitivity in leptin-resistant individuals.

The present invention discloses a compound represented by formula (I), a preparation method and application thereof, or a pharmaceutically acceptable salt, stereoisomer, isotope-labeled substance, solvate, polymorph or prodrug thereof, which can effectively inhibit the catalytic activity of histone deacetylase 6, has a high selectivity gap for other subtypes, and has anti-proliferative ability against tumor cells. It can be used to prevent and / or treat cancer, has good effects, and has low toxic side effects.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) or allograft rejection in subjects receiving donor cells. Also disclosed are methods enhancing regulatory T (Treg) cells for use in preventing GVHD. Also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the treated Treg cells. Also disclosed are enhanced Treg cells produced by the disclosed methods that have been engineered to express chimeric antigen receptor (CAR) polypeptide cells.

The invention discloses a naphthalene type chalcone compound and a preparation method and application thereof, and relates to the technical field of medicinal chemistry, and the structural formula of the naphthalene type chalcone compound is shown in the specification. Wherein part of the compounds have a good inhibition effect on HDAC6 protein, can obviously inhibit proliferation of tumor cells, and can be used for developing tumor treatment drugs related to abnormal expression of HDAC6 activity.

The invention relates generally to field of cancer biology. Provided herein are methods of inhibiting epithelial-mesenchymal transition (EMT) and for inhibiting or preventing metastasis in a cancer cell, the methods comprising contacting the cancer cell with an effective amount of a histone deacetylase 6 (HDAC6) inhibitor and a glycogen synthase kinase-3[3 (GSK30) inhibitor. Methods of screening for an inhibitor of EMT comprising a reporter cell line, which comprises a ZEB1 inducible construct, and an epithelial gene reporter construct are also provided herein.

The invention belongs to the technical field of biological medicine, and particularly relates to an N-aryl substituted amide as a novel HDAC6 (histone deacetylase 6) inhibitor and application of the N-aryl substituted amide in preparation of antitumor drugs. A compound shown as a formula (I) is screened and synthesized on the basis of an artificial intelligence technology; the compound shows excellent inhibitory activity on HDAC6, and can be used for efficiently inhibiting HDAC6 and / or HDAC1; in addition, anti-tumor cell proliferation evaluation further reveals that the compound can significantly inhibit proliferation of tumor cells. Based on the excellent enzyme inhibition activity and the cellular level anti-proliferation effect, the compound can be used for preparing medicines for treating tumors, autoimmune diseases, inflammation or Alzheimer's disease, and has a wide development prospect.

The present invention relates to a novel heterocyclic inhibitor for histone deacetylase (HDAC), a novel therapeutic agent for HDAC-associated diseases, and a pharmaceutical composition comprising same. More specifically, a compound according to the present invention exhibits a more selective and effective inhibitory activity with respect to HDAC6 even from among HDACs, and thus can be effectively used as a therapeutic agent for various HDAC6-associated diseases such as cancer, inflammatory diseases, autoimmune diseases, fibrotic diseases and degenerative diseases.

This application provides a selective HDAC6 inhibitor, its preparation method, and its application, belonging to the field of medicinal chemistry. The selective HDAC6 inhibitor is a compound of Formula I or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, and L are as described herein. The compound of Formula I is a highly selective histone deacetylase 6 (HDAC6) inhibitor, which can be used for diseases caused by HDAC6 abnormalities, such as inflammatory diseases (e.g., peritonitis, inflammatory bowel disease, psoriasis) and other diseases.

The invention discloses a novel prolyl hydroxylase 2 and histone deacetylase 6 dual selective inhibitor as shown in a formula I as well as a preparation method and application thereof, and the prolyl hydroxylase 2 and histone deacetylase 6 dual selective inhibitor plays a role in relieving acute kidney injury caused by cis-platinum by simultaneously inhibiting the activity of prolyl hydroxylase (PHD2) and histone deacetylase 6 (HDAC6). The compound is expected to become a novel acute kidney injury treatment medicine.

This invention provides an HDAC6 inhibitor, its preparation method, and its use in anti-inflammatory and ulcerative colitis treatment. By linking an alkaloid structure with anti-inflammatory activity to the hydroxamic acid group of the HDAC6 inhibitor, a series of novel compounds containing alkaloid structures and exhibiting anti-ulcerative colitis activity have been developed. Experimental data show that the above compounds exhibit good inhibitory effects on HDAC6 at the enzyme level and can be used to prepare drugs for the prevention or treatment of ulcerative colitis.

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

The invention belongs to the technical field of biological medicine, and particularly relates to a novel medicine composition and application thereof. According to the present invention, the HDAC6 inhibitor, the ribonucleotide reductase inhibitor and the anti-CD20 antibody are combined for use to achieve the synergistic effect, such that the tumor inhibition effect is significantly enhanced, the medication dosage and the medication period can be improved, the side effect of the drug can be easily reduced, and the compliance of the patient on the drug can be easily improved.

This invention relates to a chemical entity that is a selective inhibitor of histone deacetylase 6 (HDAC6), a pharmaceutical composition containing the same, and a method of using the same. The chemical entity of this invention exhibits improved cellular efficacy and is useful for treating a wide range of indications.

The present invention relates to a compound of formula (I)or a pharmaceutically acceptable salt and / or solvate thereof,wherein Y1 is a 9- or 10-membered bicyclic heteroaryl, Y2 is a 5-membered heteroaryl, Z1 is selected from (C═O)—R9, S(O)—R9 and S(O2)—R9, L is an alkyl-, cycloalkyl- or heterocycloalkyl-based linker, and R1 and R9 may be various groups.The present invention further relates to a compound of formula (I) as HDAC6 inhibitor, typically for use in the treatment and / or the prevention of an HDAC6-associated disease, such as cancers, neurodegenerative diseases, neuropathies or cardiovascular diseases.

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

The present invention relates to a novel compound having a histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof, pharmaceutically acceptable salts thereof, a use thereof in the manufacture of a medicament, a pharmaceutical composition comprising the same, a preventive or therapeutic method thereof, and a method for preparing novel 1,3,4-oxadiazole triazol, wherein a novel compound having a selective HDAC6 inhibitory activity is represented by following formula I.

The present invention relates to a compound of formula (I) wherein Y1 is a 9 or 10 membered bicyclic heteroaryl group, Y2 is a 5 or 6 membered heteroaryl group or a 6 membered aryl group, L is a linker, Z1'is selected from-NR23 'R24' and a-(C3-C7) heterocycloalkyl group comprising at least one nitrogen atom, and R23 'and R24' may be different groups, or a pharmaceutically acceptable salt and / or solvate thereof. The present invention also relates to compounds of formula (I) as HDAC6 inhibitors, typically for use in the treatment and / or prevention of HDAC6-related diseases such as cancer, neurodegenerative diseases, neuropathy and cardiovascular diseases or metabolic or hormone disorders. (I).

The present invention relates to novel compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, a medicinal use thereof, and a method for preparing the same. The novel compounds according to the present invention, stereoisomers thereof or pharmaceutically acceptable salts thereof have the histone deacetylase 6 (HDAC6) inhibitory activity, and are effective in preventing or treating HDAC6-related diseases, comprising infectious diseases; neoplasm; endocrinopathy; nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; eye and ocular adnexal diseases; circulatory diseases; respiratory diseases; digestive diseases; skin and subcutaneous tissue diseases; musculoskeletal system and connective tissue diseases; and teratosis or deformities, or chromosomal aberration.