135 results about "HDAC6" patented technology

The invention provides a VEGFR2-HDAC6 dual inhibitor containing chalcone fragments as well as a preparation method and application of the VEGFR2-HDAC6 dual inhibitor, and relates to the technical field of medicinal chemistry. The invention discloses a VEGFR2-HDAC6 dual inhibitor containing chalcone fragments. The structural formula of the VEGFR2-HDAC6 dual inhibitor is shown as a formula A, according to the invention, the VEGFR2-HDAC6 dual inhibitor containing the chalcone fragment and having a novel structure is designed and synthesized by utilizing a splicing principle, the anti-proliferative activity test is carried out on cervical cancer cells Siha and chronic granulocytic leukemia cells K562, and the result shows that the VEGFR2-HDAC6 dual inhibitor containing the chalcone fragment provided by the invention has relatively good inhibitory activity on the Siha cells and the K562 cells.

The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.

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 methods of treating or preventing metabolic disease with an HDAC6 inhibitor. Also provided herein are methods of treating or preventing heart failure with preserved ejection fraction with an HDAC6 inhibitor. A variety of HDAC6 inhibitors are described herein for use in treating or preventing metabolic disease or heart failure with preserved ejection fraction. In one aspect, described herein are methods of treating a human patient by orally administering an HDAC6 inhibitor, such as an inhibitor of Formula (I) or Formula (II).

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 relates to a polypeptide targeted to valine induction, a polypeptide therapeutic agent and application thereof, the polypeptide targeted to a valine induction section is designed based on an SE14 structural domain of valine binding protein HDAC6, the amino acid sequence of the SE14 structural domain is as shown in SEQ ID NO.1, and the amino acid sequence of the polypeptide is as shown in any one of SEQ ID NO.2-SEQ ID NO.8; according to the present invention, the polypeptide is taken into the cell by using the cell-penetrating peptide, the polypeptide is combined with the valine to release the protein HDAC6 combined with the valine, and the HDAC6 not combined with the valine enters the cell nucleus to achieve the tumor inhibition effect, such that the tumor progress is inhibited by formulating the polypeptide specifically targeting the valine induction, and the tumor inhibition effect is provided; the compound has important research significance and application value in preparation of medicines for preventing and / or treating tumors.

The present invention relates to a novel heterocyclic histone deacetylase inhibitor, a new therapeutic agent for histone deacetylase-associated diseases, and a pharmaceutical composition containing the same. More specifically, the compound according to the present invention exhibits more selective and effective HDAC6 inhibitory activity against HDAC6 among histone deacetylases (HDACs), and can therefore be usefully used as a therapeutic agent for various diseases such as HDAC6-associated diseases, for example, cancer diseases, inflammatory diseases, autoimmune diseases, fibrotic diseases, and degenerative diseases.

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 belongs to the field of pharmaceutical chemistry technology, and specifically relates to a pyridine compound containing N-hydroxy-benzamide, a preparation method and an application. The pyridine compound containing N-hydroxy-benzamide of the present invention is a compound shown in Formula I or a pharmaceutically acceptable salt thereof: the compound of the present invention can effectively inhibit HDAC6, and has an inhibitory effect on the proliferation and cloning of tumor cells, and has a promoting effect on the apoptosis of tumor cells. Therefore, it can be used to prepare HDAC6 inhibitors, and can also be used as a new compound for the preparation of anticancer drugs. Therefore, the present invention can provide new research and development directions and structural options for the development of HDAC6 inhibitors or anti-tumor drugs.

The present invention relates to a novel compound having histone deacetylase 6 (HDAC6) inhibitory activity, an isomer thereof or a pharmaceutically acceptable salt thereof, their use for preparing therapeutic drugs; a pharmaceutical composition containing them and a therapeutic method using the composition; and a preparation method thereof. The novel compound, its isomer or a pharmaceutically acceptable salt thereof according to the present invention has HDAC6 inhibitory activity, which effectively prevents or treats HDAC6-mediated diseases, including cancer, inflammatory diseases, autoimmune diseases, nervous system diseases or neurodegenerative diseases.

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 invention belongs to the technical field of medicine, and discloses an application method of an HDAC6 and HSP90 bifunctional inhibitor, a double-target drug can act on two different targets at the same time, so that a synergistic effect is achieved in the aspects of regulating a signal channel, regulating physiological functions and the like, and the treatment effect is improved. Due to the fact that the double-target medicine acts on the two targets at the same time, the drug resistance appearing in disease development is reduced, and the lasting time of the curative effect of the medicine is prolonged. By acting on the two targets at the same time, the double-target medicine can achieve the same curative effect under the lower dosage, and therefore the influence of the side effect on a patient is reduced. The double-target drug has the advantages of better curative effect, low drug resistance, small side effect, personalized treatment and the like. According to the present invention, two targets such as HSP90 and HDAC6 are combined, and an HDAC6 and HSP90 dual-function inhibitor is reported, and is used for treating inflammatory bowel diseases, such as ulcerative colitis and Crohn disease.

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.

The present invention relates to a novel compound having histone deacetylase 6 (HDAC6) inhibitory activity, a stereoisomer thereof, and a pharmaceutically acceptable salt thereof; the use thereof for preparing a medicament; a pharmaceutical composition comprising the same; method for preventing or treating the same, and method for preparing a novel 1, 3, 4-oxadiazole triazole, in which a novel compound having selective HDAC6 inhibitory activity is represented by the following formula I: [Formula I] # imgabs0 #

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.

The invention provides a benzimidazole fragment-containing compound as well as a preparation method and application thereof, and relates to the technical field of medicinal chemistry. The structural formula of the compound containing the benzimidazole fragment is as shown in the formula I. The compound containing the benzimidazole fragment has an inhibitory effect on HDAC6 and is relatively high in inhibitory activity.