61 results about "HDAC6" patented technology

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.

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.

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.

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.

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 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 application relates to a PI3K alpha / HDAC6 subtype selective dual inhibitor, which is a compound with general formula (I) as follows and pharmaceutically acceptable salts or solvates thereof: The present application also relates to the use of the PI3K alpha / HDAC6 subtype selective dual inhibitor in the preparation of antitumor drugs. The compound with general formula (I) of the present application is a subtype selective PI3K alpha / HDAC6 dual inhibitor, which has structural units required for inhibiting PI3K alpha and HDAC6, has significant PI3K alpha and HDAC6 dual inhibition activity, can avoid the shortcomings of PI3K and HDAC inhibitors and non-selective pan-PI3K / HDAC dual inhibitors in antitumor efficacy and toxicity, and can overcome the problems of drug-drug interactions, cumulative toxicity, complex pharmacokinetics, poor patient compliance and the like in the combination therapy of PI3K inhibitors and HDAC inhibitors, so the subtype selective PI3K alpha / HDAC6 dual inhibitor is particularly valuable in the treatment of proliferative diseases such as cancer.

Compounds having activity as inhibitors of HDAC6 are provided. The compounds have Structure (I):or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein X, R1, R2, R3, and Rb are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of HDAC6 are also provided.

The present disclosure provides histone deacetylase 6 (HDAC6)-activated macrophages, compositions comprising HDAC6-activated macrophages, methods of making HDAC6-activated macrophages, and methods of treating diseases, e.g., cancer, by administering a therapeutically effective amount of HDAC6-activated macrophages.

Compounds having activity as inhibitors of HDAC6 are provided. The compounds have Structure Formula (I): or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein X, R1, R2, R3, and Rb are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of HDAC6 are also provided.

This invention discloses a naphthyl chalcone compound, its preparation method, and its application, relating to the field of medicinal chemistry. The structural formula of the naphthyl chalcone compound is shown below. This invention utilizes computer-aided drug design to obtain a series of naphthyl chalcone compounds, some of which exhibit good inhibitory effects on HDAC6 protein and can significantly inhibit the proliferation of tumor cells. These compounds can be used to develop tumor therapeutic drugs related to abnormal expression of HDAC6 activity.

The invention relates to compounds of Formula (I) as described herein, useful as histone deacetylase 6 (HDAC6) inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds and to their use in therapy.

This invention discloses a high-affinity chimeric peptide sensor and a ubiquitin detection method and kit, belonging to the field of biodetection technology. To address the problems of low affinity and poor selectivity in existing ubiquitin detection tools, this invention obtains a V1091L mutant of the HDAC6 ZnF fragment through multidimensional mutagenesis, and integrates other ubiquitin-binding domains using AI and computer simulation to construct a chimeric peptide sensor. Its Kd with monoubiquitin is less than 50 nM, and it can specifically bind some free ubiquitin. This invention also provides a detection method based on this sensor, enabling the detection of free ubiquitin and total ubiquitin through direct or competitive assays. It can calculate the amount of conjugated ubiquitin, determine deubiquitinase activity, and screen ubiquitin pathway regulators. A kit incorporating this sensor is also provided. The sensor of this invention exhibits high affinity and high selectivity, and the detection method requires no complex instruments, making it suitable for complex biological samples and high-throughput detection. It can also distinguish intact free ubiquitin in serum, providing a new tool for basic ubiquitin research and clinical detection, and has significant application value.

The present invention relates to acylhydrazides obtained in situ by enzymatic hydrolysis of the parent prodrug 2-(difluoromethyl)- or 2-(trifluoromethyl)-1,3,4-oxadiazole, in histone deacetylase 6 (HDAC6).

The invention belongs to the technical field of biological medicine, and relates to a benzimidazole derivative serving as a novel HDAC inhibitor, a pharmaceutical composition containing the benzimidazole derivative, a pharmaceutical preparation containing the benzimidazole derivative and medical application of the benzimidazole derivative. The benzimidazole derivative is a compound with a structure as shown in a formula (I), has excellent HDAC inhibitory activity, can inhibit HDAC6 and / or HDAC1 with high strength, and shows excellent HDAC6 selectivity. Meanwhile, the compound disclosed by the invention shows remarkable anti-tumor cell proliferation activity. The compound provided by the invention can be used as a therapeutic drug for tumors, autoimmune diseases, inflammation or Alzheimer's disease.

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, X and W are carbon or nitrogen, L1 and L2 are simple bonds or linkers, and Z1 and R1 are hydrogen or 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.

This invention is a divisional application of patent application number 202311457833.6. This invention belongs to the field of compound synthesis technology, specifically relating to an indole compound that targets and inhibits HDAC6, its preparation method, and its applications. The indole compound that targets and inhibits HDAC6 of this invention is a compound represented by Formula I or a pharmaceutically acceptable salt thereof. Experimental results show that the indole compound that targets and inhibits HDAC6 provided by this invention not only has superior selective inhibitory activity against HDAC6 protein but also inhibits the proliferation of gastric cancer cells in a concentration-dependent manner. Therefore, the compound of this invention has good application prospects in the preparation of inhibitory drugs based on the HDAC6 target and drugs that inhibit the proliferation activity of gastric cancer cells, and is of great significance in the development of anti-tumor drugs and the treatment of related diseases.

The present invention relates to chemical entities that are selective inhibitors of histone deacetylase 6 (HDAC6), pharmaceutical compositions comprising the chemical entities, and methods of using the chemical entities. The chemical entities according to the invention have improved cellular potency and are useful for the treatment of a wide range of indications.

Provided herein are compounds useful for binding to one or more histone deacetylase enzymes (HDACs). The present application further provides radiolabeled compounds useful as a radiotracer for position emission tomography imaging of HDAC. Methods for prepared unlabeled and labeled compounds, diagnostic methods, and methods of treating diseases associated HDAC are also provided.

This invention provides a benzothiadiazine compound that inhibits histone deacetylases, its preparation method, and its applications. The general structural formula is shown in Formula (I), or an isomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug thereof. The benzothiadiazine compound of this invention has a novel structure and, as an inhibitor of histone deacetylases HDAC6 and HDAC1, can effectively inhibit the proliferation of K562 (human chronic myeloid leukemia cells) and NCI-H929 (human myeloma cells). It exhibits low cytotoxicity to normal cells and low potential cardiac risk, and holds promise as a highly effective and low-toxicity antitumor therapeutic agent.