65 results about "Histone deacetylase" patented technology

Provided herein is the pharmaceutical combination comprising an embryonic ectoderm development (EED) inhibitor and another inhibitor selected from the group consisting of a histone deacetylase (HDAC) inhibitor, a JAK inhibitor and a BCL2 / BCL-XL inhibitor; wherein the EED inhibitor is a compound of Formula (I) or the pharmaceutically acceptable salt or solvate thereof. The EED inhibitor combined with another inhibitor selected from the group consisting of a histone deacetylase (HDAC) inhibitor, a JAK inhibitor and a BCL2 / BCL-XL inhibitor produces synergistic effects over a single use of either the EED inhibitor or said another inhibitor.

The preparation method comprises the following steps: by taking alkynol (compound II) as a raw material, reacting with methoxycarbonyl methylene triphenyl phosphorus under the action of an oxidizing agent to obtain a methyl ester compound (compound III), hydrolyzing under the action of alkali to obtain acid (compound IV), finally reacting with alkali, and filtering to obtain the crotonyl acylation detection probe. And freeze-drying to obtain the probe molecule (compound I). According to the present invention, a chemical probe (compound I) having an alkynyl group is applied in a cell, the alkynyl group is selectively loaded on a target protein at a specific modification site through a metabolic marker, and a fluorescent dye can be orthogonally linked to the modification site through a bio-orthogonal chemical reaction, therefore, the probe is used for performing fluorescence imaging on crotonyl protein in cells and identifying crotonyl modified substrates and sites, and the crotonyl sites regulated and controlled by histone deacetylase (HDACs) can be determined by utilizing the probe through quantitative chemical proteomics.

The invention discloses a recombinant genetically engineered bacterium for producing a micafungin precursor FR901379 and an application of the recombinant genetically engineered bacterium. The recombinant genetically engineered bacterium for producing the micafungin precursor FR901379 is obtained by performing overexpression on an epigenetic modification factor in a phomopsis sheathing genome and performing screening to obtain the recombinant genetically engineered bacterium for producing the micafungin precursor FR901379. The epigenetic modification factor comprises a histone methyltransferase (Dot 1), a histone methyltransferase (Set2) or a histone deacetylase (Rpd3). The yield of FR901379 produced by the engineering strain is increased by 40% compared with that of an original strain. The method disclosed by the invention has the characteristics of simplicity and convenience in operation, high transformation efficiency and good genetic stability.

The invention relates to methods for producing preparations comprising recombinant adeno-associated virus (rAAV) particles. More particularly, the present invention relates to methods comprising a step of contacting a host cell with a polo like kinase (PLK) modulator, a cell cycle modulator preferably an Aurora kinase modulator or a FOXM1 modulator, a microtubule modulator, a histone deacetylase (HDAC) modulator, a G protein-coupled receptor (GPCR) modulator or a JAK modulator.

The present invention discloses a photoelectrochemical biosensor for detecting histone deacetylase and a preparation method thereof, belonging to the field of photoelectrochemical analysis technology. The present invention comprises a base electrode, and CuS-BiVO4 and MnO2 sequentially modified on the surface of the base electrode. The present invention utilizes the energy band matching effect between CuS and BiVO4, and Sirt1 reacts with P Ac The specific deacetylation of MnO2 by NADH and the reduction of MnO2 by NADH enable the detection of the histone deacetylase Sirt1. This method is simple to operate and only requires simple modification of the ITO electrode surface to achieve Sirt1 detection.

The invention discloses a hydantoin thiourea compound with dual inhibition effects of an androgen receptor and histone deacetylase 6, and further discloses a pharmaceutically acceptable salt of the hydantoin thiourea compound with the dual inhibition effects of the androgen receptor and the histone deacetylase 6. The invention further discloses application of the compound in preparation of a dual inhibitor serving as an androsinesin receptor and histone deacetylase 6. The invention also discloses application of the compound in preparation of drugs for treating tumors related to androgen receptors and histone deacetylase 6. The medicine prepared from the compound has an anti-prostatic cancer effect, provides a new direction for the research of the anti-prostatic cancer medicine, and is of great significance to the development of the anti-prostatic cancer medicine.

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 treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The present disclosure relates to pharmaceutical compositions comprising a synthetic transcription elongation factor (SynTEF) and an epigenetic inhibitor (e.g., a histone deacetylase (HDAC) inhibitor). As detailed herein, the disclosed compositions and combinations can be used to target FGF14b in Friedreich's ataxia (FRDA / FA), SCA27b, and other GAA-repeat based diseases.

The invention relates to pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivatives as well as a synthesis method and application thereof. The pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivatives have structural general formulas I and II. The pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivative disclosed by the invention shows remarkable inhibitory activity on phosphatidylinositol-3-kinase and histone deacetylase. The pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivative disclosed by the invention can be used as a phosphatidylinositol-3-kinase / histone deacetylase double-target inhibitor, and is used for preparing medicines for treating various malignant tumors jointly mediated by phosphatidylinositol-3-kinase and histone deacetylase.

An isolated myocyte enhancer factor-2 (MEF2) binding molecule comprising an amino acid sequence of: X1 X2 X3 X4 A X6 A S X9 X10 V K X13 X14 L X16 E X18 X19 L X21 K X23 X24 X25 X26, in which X1 is S or G, or is removed; X2 is K or R; X3 is R or E; X4 is S or R; X6 is V or I; X9 is S or T; X10 is V or E; X13 is Q, M, or L; X14 is K or R; X16 is A or Q; X18 is V or F; X19 is I, V, or L; X21 is K, N, or S; X23 is Q, K, or S; X24 is Q or A, or is removed; X25 is A or T, or is removed; and X26 is A or K. In addition, use of the isolated MEF2 binding molecule to inhibit binding of histone deacetylase (HD AC) and MEF2 in a cell, and to inhibit HDAC- induced suppression of MEF2-dependent gene expression in a cell.

The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by aberrant activity of at least one class IIa histone deacetylase (HDAC4 / 5 / 7 / 9).

Provided herein are compositions suitable for treating chemically induced eye damage comprising (a) a nonsteroidal anti-inflammatory drug (NSAID), (b) a histone deacetylase (HDAC) inhibitor and (c) an angiotensin converting enzyme (ACE) inhibitor and, optionally, (d) a water-soluble vitamin. Methods of using provided compositions to treat ocular toxicity and corneal damage following exposure to chemical agents (e.g., mustard gas) are also provided.

This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to a compound based on the 6-methylfurano[2,3-d]pyrimidine-4(3H)-one structure, its preparation method, and its applications. The compound provided by this invention, based on the 6-methylfurano[2,3-d]pyrimidine-4(3H)-one structure, enhances the chelation effect between the compound and zinc ions in histone deacetylases by combining the pharmacophore of a DNA methyltransferase 3A inhibitor with an isohydroxamic acid fragment, thus exhibiting strong HDAC inhibitory activity while maintaining DNMT3A inhibition. The compound provided by this invention shows significantly higher inhibitory activity against human non-small cell lung cancer cells H460 than against H460 DNMT3A-HDAC6 double knockout cells, demonstrating in vivo activity against human non-small cell lung cancer and possessing application value as a therapeutic agent for diseases and disorders related to DNMT3A and HDAC6.

The present disclosure provides compounds represented by Formula I:and pharmaceutically acceptable salts, solvates, e.g., hydrates, and prodrugs thereof, wherein X and n are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat diseases and conditions, e.g., cancer, wherein inhibition of HDAC provides a benefit.

The application discloses a crotonylation detection probe and a preparation method and application thereof, and the preparation method comprises the following steps: taking an alkyne alcohol (compound II) as raw material, reacting with methoxycarbonylmethylidene triphenyl positive phosphorus under the action of an oxidant to obtain a methyl ester compound (compound III), hydrolyzing the methyl ester compound (compound III) under the action of alkali to obtain an acid (compound IV), and finally reacting the acid (compound IV) with alkali, filtering and freeze-drying to obtain the probe molecule (compound I). The chemical probe (compound I) with an alkyne group is applied in cells, the alkyne group is selectively loaded on target proteins at specific modification sites through metabolic labeling, and through a bio-orthogonal chemical reaction, a fluorescent dye can be orthogonally connected to the modification site, so that the probe is used for fluorescent imaging of crotonylation proteins in cells and identification of crotonylation modification substrates and sites, and by using the probe, crotonylation sites regulated by histone deacetylases (HDACs) can be determined through quantitative chemical proteomics.

The present invention belongs to the field of biomedical technology and discloses a method for screening drugs targeting histone deacetylase SIRT6 regulators. Based on testing the affinity between SIRT6 protein and small molecules with SYPRO Orange Protein Gel Staining Solution, this method constructs a drug screening model to screen for SIRT6 regulator-targeting drugs. The drug screening model constructed by the present invention is applicable to screening monomeric compound drugs with strong affinity effects (including agonists and inhibitors) on histone deacetylase SIRT6, and the action sites of the screened compounds are clear; the screening of monomeric compound drugs using this drug screening model has the advantages of high throughput, small protein consumption, low concentration, low cost, strong specificity, and convenient operation, providing a new and effective option for the screening of histone deacetylase SIRT6 regulators in this field, having good application prospects, and successfully screening out monomeric compound drugs with strong targeting effects on SIRT6 protein.

The present invention discloses a thiohydantoin compound having dual inhibitory effects on the androgen receptor and histone deacetylase 6. The present invention also discloses a pharmaceutically acceptable salt of the thiohydantoin compound having dual inhibitory effects on the androgen receptor and histone deacetylase 6. The present invention also discloses the use of the compound in preparing a dual inhibitor of the androgen receptor and histone deacetylase 6. The present invention also discloses the use of the compound in preparing a drug for treating tumors associated with the androgen receptor and histone deacetylase 6. The drug prepared using the compound has an anti-prostate cancer effect, providing a new direction for the research of anti-prostate cancer drugs and having important significance for the development of anti-prostate cancer drugs.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a compound based on a 6-methylfuro [2, 3-d] pyrimidine-4 (3H)-ketone structure and a preparation method and application thereof. According to the compound based on the 6-methylfuro [2, 3-d] pyrimidine-4 (3H)-one structure, a pharmacophore of a DNA methyltransferase 3A inhibitor is spliced with a hydroxamic acid fragment, the chelation of the compound and zinc ions in histone deacetylase is increased, and the compound shows a relatively strong HDAC inhibition effect while keeping the inhibition effect on DNMT3A. The inhibitory activity of the compound provided by the invention on human non-small cell lung cancer cells H460 is far higher than that of H460DNMT3A-HDAC6 double knockout cells, and the compound shows the activity of resisting human non-small cell lung cancer in vivo, and has application value as a drug therapeutic agent for treating diseases and disorders related to DNMT3A and HADC6.

The present invention relates to some crystal forms for a cinnamic compound, BMX, which is an inhibitor of histone deacetylase (HDAC), useful as an agent for the prevention or treatment of diseases associated with HDAC, including for treating tumor or cell proliferative diseases, diabetes mellitus, or neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Spinocerebellar Ataxias (SCA) and human spinal muscular atrophy (SMA). Also provided are a method for preparing the crystal forms and pharmaceutical compositions comprising the crystal forms.

Histone deacetylases inhibitors (HDACbls) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC6 provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease including peripheral neuropathies such as Charcot Marie Tooth disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.

The application discloses histone deacetylase SmHDA6 and application of an encoding gene thereof in regulating accumulation of salvianolic acid. The application provides a histone deacetylase SmHDA6 for regulating biosynthesis of salvianolic acid in Danshen, wherein an amino acid sequence is shown as SEQ ID NO. 4, and a nucleotide sequence is shown as SEQ ID NO. 1. In the application, the SmHDA6 has a Histone deacetylase domain conservative functional domain for exerting histone deacetylation, is clustered in a Type I (RPD3-like superfamily) subfamily in the HDA family, expression amounts of the SmHDA6 gene in different parts of Danshen are obviously positively correlated with salvianolic acid content, and expression of the SmHDA6 gene is significantly up-regulated after being induced by ABA, MeJA and SA. Knocking out the SmHDA6 gene by a gene editing technology can significantly improve salvianolic acid content in Danshen, because knocking out the SmHDA6 gene activates expression of genes in a salvianolic acid metabolic pathway, and then increases biosynthesis of the salvianolic acid. Therefore, the SmHDA6 can regulate accumulation of the salvianolic acid in Danshen, can be applied to engineering bacteria and genetic engineering breeding of Danshen with high salvianolic acid content, and has great application value.

The invention discloses a pyrimidine-hydroxamic acid compound as well as a preparation method and application thereof. The compound has a general formula as shown in a formula I. The compound can be used as a small-molecule inhibitor of histone deacetylase (HDAC), has strong anti-malaria activity, has a remarkable killing effect on various wild and drug-resistant plasmodium, and has the potential of being developed into an anti-malaria drug with a novel action mechanism.

The present invention provides a type-I type bioactive photosensitizer targeting HDAC, and its preparation method and application in living tumor treatment. The photosensitizer molecular structure is as follows: the core skeleton is quinoxalinone, which is obtained by condensation cyclization, nucleophilic substitution, aldol condensation, ester hydrolysis and amidation, Suzuki coupling reaction by o-phenylenediamine and its derivatives. Only one column chromatography is required during the whole synthesis process, and the preparation is simple. The molecule of the present invention has strong fluorescence emission under blue light radiation, and can produce a large amount of reactive oxygen free radicals such as hydroxyl radicals and superoxide radicals at the same time. The compound of the present invention can also be used for photodynamic therapy of tumor cells, and can also be used to prepare nanoparticles using polyethylene glycol and then be injected intravenously to exert molecular targeted therapy and photodynamic therapy in vivo. In addition, the material of the present invention can induce cell ferroptosis by inhibiting histone deacetylase expression, alleviate hypoxic microenvironment, improve photodynamic therapy effect, and has good application prospects.

The invention discloses an application of histone deacetylase HDA108 in regulation and control of plant C4 photosynthetic metabolism. By inhibiting the expression of the gene HDA108 in the corn, the expression of C4 related photosynthetic genes in the corn can be improved. The invention provides an effective gene resource for enhancing corn C4 photosynthetic metabolism.

The invention discloses a 2, 4, 7-trisubstituted quinazoline derivative as well as a synthesis method and application thereof, and belongs to the field of organic synthesis and medicinal chemistry. The compound has an innovative molecular structure, can simultaneously inhibit histone lysine demethylase (KDM) and histone deacetylase (HDAC) in a targeted manner, and represents a novel double-target epigenetic regulating agent. The preparation method adopts a modular synthesis strategy, constructs a core structure through a three-step continuous functionalization reaction, has the characteristics of simple and convenient process, easily available raw materials, mild reaction conditions and the like, and is particularly suitable for industrial enlarged production. In-vitro activity evaluation shows that part of the compounds have nanomole-level inhibitory activity on double targets, can be used as lead compounds for developing novel antitumor drugs after structural modification and pharmacophore optimization, and show important application value in the field of epigenetic targeted therapy.

To provide methods of treating diseases.SOLUTION: The present disclosure provides compounds represented by Formula (I) and pharmaceutically acceptable salts, solvates, e.g., hydrates, and prodrugs thereof, where X and n are defined as described in the specification. The present disclosure also provides compounds of Formula (I) used to treat diseases and conditions, e.g., cancer, in which inhibition of HDAC provides a benefit. In one aspect, the present disclosure provides compounds having any one of Formulas I-V below, and pharmaceutically acceptable salts, solvates, e.g., hydrates, and prodrugs thereof, collectively referred to as "Compounds of the Disclosure". The Compounds of the Disclosure are histone deacetylase inhibitors.SELECTED DRAWING: Figure 1

The invention belongs to the field of medicines, and relates to a quinoline derivative as well as a preparation method and application thereof. The quinoline derivative is selected from at least one compound in a structure as shown in a formula I, or a tautomer or a mixture thereof, or a prodrug thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof. A DNA methyltransferase inhibitory activity test, a histone deacetylase inhibitory activity test and a tumor cell proliferation inhibitory activity test on the compound provided by the invention prove that the quinoline derivative provided by the invention is a potential antitumor drug with inhibitory activity on DNA methyltransferase and histone deacetylase. The raw materials of the compound are easy to obtain, the preparation method is simple, and experiments prove that the compound has a good anti-cancer effect and has a good application prospect in the field of design, research and development of anti-tumor drugs.

Provided is a quinolyl-containing compound as shown in general formula (I) or (II) or a pharmaceutically acceptable salt, a solvate, an active metabolite, a polymorph, an isotopic label, or an isomer thereof, and further provided are a pharmaceutical composition comprising the compound and use of the compound and the pharmaceutical composition. The provided compound has a dual molecule function, can serve as multi-target inhibitors of novel tyrosine kinase / histone deacetylase, can simultaneously achieve the effect of two inhibitors, has excellent biological activity and pharmacokinetic properties, and has the application potential particularly in the field of treatment of tumors.

The present disclosure provides compounds represented by Formula I:and pharmaceutically acceptable salts, solvates, e.g., hydrates, and prodrugs thereof, wherein X and n are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat diseases and conditions, e.g., cancer, wherein inhibition of HDAC provides a benefit.

The invention discloses application and application of an MSP gene to regulation and control of the number of grains per panicle of rice, the CDS sequence of the MSP gene is shown as SEQ ID No.1, and the amino acid sequence of encoded protein is shown as SEQ ID No.2. The MSP gene serves as a transcription inhibition factor to interact with a co-inhibition factor OsTPR2, specifically binds to a P4 site containing CArG-box of a downstream target gene TAWAWA1 promoter, recruits histone deacetylase to inhibit TAWAWA1 expression, and is used for regulating and controlling the number of grains per panicle of rice. The rice inflorescence morphology is regulated and controlled, and the grain number per ear is regulated and controlled. According to the invention, a promoter of a glume protection / glume specific expression gene is fused with an MSP gene CDS to construct a fusion vector, and an msp mutant is transformed, so that an incomplete complementary plant with normal glume protection, recovered grain size and maturing rate and higher grain number per ear than that of a wild type is obtained, and the defects that the grain of the msp mutant becomes small and the like are overcome. The rice inflorescence development regulation theory is expanded, and a theoretical basis and a new thought are provided for high-yield molecular breeding.