81 results about "HDAC inhibitor" patented technology

A combination of an immune cell that expresses a receptor that recognizes a tumor antigen and a benzamide-based HDAC inhibitor. The invention further discloses a kit containing the immune cells and the benzamide HDAC inhibitor and a method for combined treatment of diseases such as cancer.

The present application relates to a method for inducing pluripotent cells to proliferate and / or differentiate into megakaryocyte progenitor cells (MKPs), comprising adding a human platelet lysate (hPL) and an HDAC inhibitor to an MKP differentiation medium. The present application also provides a culture medium used in the method, and a composition comprising the culture medium.

The present invention relates to an expansion culture method for natural killer cells and, more particularly, to an expansion culture method for natural killer cells, wherein the cultured natural killer cells are treated with an HDAC inhibitor. According to the present invention, when natural killer cells are subjected to in vitro expansion culture, the cells can be restrained from undergoing cell death, resulting in a remarkable improvement in the viability and production yield of the cells. Thus, natural killer cells, which are needed for cell therapy, such as cancer therapy, etc., can be obtained effectively.

The invention discloses an MEK / HDAC double-target inhibitor as well as a synthesis method and application thereof, and belongs to the technical field of medicines. Through molecular docking and in-vitro thermodynamic migration experiments, the applicant finds that the inhibitor not only can stabilize MEK and HDAC proteins, but also can be specifically combined with the MEK and HDAC proteins in an intracellular environment; protein immunoblotting experiments find that the inhibitor can inhibit reactivation of ERK, overcomes the limitation of a single-target inhibitor in curative effect and activity, and significantly improves the drug resistance problem of trametinib in ovarian cancer treatment and various EGFR-TKI treatment in non-small cell lung cancer treatment; furthermore, an in-vitro anti-tumor activity experiment shows that the IC50 value of the MEK / HDAC inhibitor on tumor cells from human ovarian cancer and various lung cancers is 0.07-10 mu M, and the MEK / HDAC inhibitor has a wide and remarkable proliferation inhibition effect.

A method for reprogramming native CD4+ T-cells is provided. The method comprises incubating the CD4+ T-cells with a Class 1 HDAC inhibitor for a period of time sufficient to increase cytotoxicity of the CD4+ T-cells in comparison to the cytotoxicity of native CD4+ T-cells. The method may be utilized to prepare cytotoxic tumor infiltrating CD4+ T-cells for use to treat cancer, including MHC-I deficient cancers.

This invention belongs to the field of pharmaceutical preparation technology, specifically relating to an HDAC inhibitor based on a tyrosine backbone, its synthesis method, and its application. The invention uses L-tyrosine as the backbone, with its aromatic ring as the Cap region, linked by a flexible alkyl chain via an ether bond, and terminated by an isohydroxamic acid group (ZBG). The tyrosine backbone provides a rigid structure, reducing entropy loss and enhancing hydrophobic interactions with the HDAC surface. By introducing substituents (such as halogens, methyl groups, etc.) onto the tyrosine benzene ring, the affinity with the HDAC active pocket is further optimized. The prepared compound b19 exhibits an HDAC inhibition capacity of 100%. 50 The concentration reached 26.8 nM, exhibiting superior antitumor activity compared to SAHA, especially against solid tumors such as HeLa cells with IC50. 50 It is 0.55 μM.

The present application relates to a method for inducing proliferation and / or differentiation of pluripotent cells into megakaryocyte progenitor cells (MKP), comprising adding human platelet lysate (hPL) and an HDAC inhibitor to an MKP differentiation medium. The invention also provides a culture medium used by the method and a composition containing the culture medium.

Provided are methods and compositions for the treatment of cancer. The methods comprise administering to a subject an HDAC inhibitor and an immunotherapeutic agent. In certain instances the immunotherapeutic is an NK cell or a chimeric antigen receptor NK cell.

The disclosure relates to crystalline forms of an HDAC inhibitor, pharmaceutical compositions thereof, and methods of treating cancers, including cancers having modified STK11 activity or expression, by administering an effective amount of the crystalline forms or compositions.

A method for treating Ewing's sarcoma in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of (E)-3-(2-(4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)pyrimidin-5-yl)-N-hydroxyacrylamide or a pharmaceutically acceptable salt thereof.

The invention discloses an STAT3 / NQO1 / HDAC three-target compound as well as a synthesis method and application thereof, the compound is a compound with a structural general formula shown as a formula I or pharmaceutically acceptable salt thereof, and the structural formula of the compound shown as the formula I is shown in the specification. The invention also specifically discloses a synthesis method of the compound and application of the compound in preparation of a medicine for treating triple negative breast cancer. The STAT3 / NQO1 / HDAC three-target compound synthesized by the invention is an effective NQO1 substrate, can inhibit the activity of STAT3 and HDAC at the same time, is used for preparing a therapeutic drug for resisting triple-negative breast cancer, effectively overcomes the problem of drug resistance of a single HDAC inhibitor, and has a better application prospect in the aspect of clinical triple-negative breast cancer treatment.

The invention relates to protected HDAC inhibitor compounds of formula I, in which Y, Ar1, Ar2, X, R1 and R2 are as defined herein. In aspects, the inventions relates to use of the compounds, and to methods of deprotecting the compounds.

The invention provides an application of a composition, a culture medium additive or a culture medium in amplifying hematopoietic stem cells or preparing products for amplifying the hematopoietic stem cells. On the first aspect, the invention provides application of the composition, the culture medium additive or the culture medium to hematopoietic stem cell amplification or hematopoietic stem cell amplification product preparation. The composition comprises quininostat and resveratrol. The culture medium additive comprises a composition; the culture medium comprises a basic culture medium and an additive, wherein the additive comprises the composition. By screening the combination of a specific HDAC inhibitor and other various different small molecule compounds, the proportion of CD34 +, CD34 + CD90 + and CD34 + CD90 + EPCR + cells of HSC after in-vitro amplification can be obviously improved at a lower working concentration, namely, the proportion of hematopoietic stem cells and long-acting hematopoietic stem cells can be improved.

This application provides the use of a composition, culture medium additive, or culture medium in expanding hematopoietic stem cells or preparing products containing expanded hematopoietic stem cells. A first aspect of this application discloses the use of a composition, culture medium additive, or culture medium in expanding hematopoietic stem cells or preparing products containing expanded hematopoietic stem cells. The composition includes quinsinostat and resveratrol; the culture medium additive includes the composition; the culture medium includes a basal medium and an additive, the additive including the composition. By screening specific HDAC inhibitors and combinations of various other small molecule compounds, the CD34 concentration of HSCs after in vitro expansion can be significantly increased at lower working concentrations. + CD34 + CD90 + and CD34 + CD90 + EPCR + The proportion of cells, that is, the proportion of hematopoietic stem cells and long-acting hematopoietic stem cells, can be increased.

The present technology generally relates to methods of treating social deficits with HDAC inhibitors. Select embodiments of the present technology include a method for treating organophosphate induced social deficits in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an HDAC inhibitor selected from the group consisting of valproic acid, butyric acid, BRD-6929, RGFP966, pharmaceutically acceptable salts thereof, and combinations thereof. The subject may have been diagnosed with a disease or disorder characterized by social deficits, such as autism spectrum disorder. The subject may be monitored for a change in the severity of social deficits.

Provided herein are methods of treating and / or managing cancer, comprising administering to a patient Compound A, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof. Additionally, provided herein are methods of treating and / or managing cancer, comprising administering to a patient Compound A, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, in combination with a second active agent selected from the group consisting of an anti-CD20 antibody, an HDAC inhibitor, a proteasome inhibitor, an anti-CD38 antibody, an anti-SLAMF7 antibody, a nuclear export inhibitor, a BCL-2 inhibitor, and an immune checkpoint inhibitor. Also provided herein are combination therapies for treating and / or managing cancer, further comprising dexamethasone as a third active agent.

Provided herein are methods and formulations for reducing viability of a cancer or enhancing susceptibility of a cancer to an anti-cancer agent. The method includes administering to the subject an effective amount of an anti-parasitic agent and an autophagy inhibitor to the subject. Additionally or optionally, the method further includes administering to the subject the anti-cancer agent. Also provided herein are formulations for the treatment of cancers, particularly cancers that are unresponsive to anti-cancer agents. The formulation includes at least two agents selected from the group consisting of an anti-parasitic agent, an autophagy inhibitor and an HDAC inhibitor; and a pharmaceutically acceptable excipient.

The application discloses a kind of hydroxamic acid double-target compound derivatives and application thereof.The double-target derivative designed in the application has obvious inhibitory activity to WDR5 protein and HDAC protein, can be used as WDR5, HDAC double-target inhibitor, is used for treating diseases related to WDR5, HDAC, aims at improving the therapeutic effect of existing HDAC inhibitor.The small molecule shows good activity in various experiments, and is expected to be developed into specific antitumor drugs.

The present disclosure generally relates to solid state forms of an histone deacetylases (HDACs) inhibitor and pharmaceutical compositions comprising the solid state crystalline forms and pharmaceutically acceptable excipients, and methods for preparing and using the solid state forms and the pharmaceutical compositions thereof.

Described herein are methods useful for the treatment of cancers in a canine subject with a pharmaceutical compositions comprising HDAC inhibitors, Rapamycin, Dasatinib, Lapatinib, Trametinib, Vorinostat, Imatinib, Crizotinib, Sorafenib, and combinations thereof. Also described herein are methods for identification of subjects with cancers that will benefit from administration of the pharmaceutical compositions comprising HIDAC inhibitors, Rapamycin, Dasatinib, Lapatinib, Trametinib, Vorinostat, Imatinib, Crizotinib, Sorafenib, and combinations thereof. In certain aspects, the methods described herein further comprise administering a therapeutically effective amount of at least one additional anti-cancer agent.

The invention relates to the field of biomedicine, in particular to a protein polypeptide combined with type I histone deacetylase (HDACs) and capable of improving the solid tumor resisting curative effect of an HDAC inhibitor. The protein polypeptide combined with the I-type HDACs is developed on the basis of a liver-type phosphofructokinase (PFKL) protein sequence, the protein polypeptide is directly combined with the I-type HDACs through a Thr562 site, the targeting chelation stability of an HDAC inhibitor Romidepsin on zinc ions in the HDACs is promoted, and the anti-tumor drug effect of the Romidepsin can be remarkably improved. The invention provides an effective tool for solving the problem of insufficient curative effect of the HDAC inhibitor Romidepsin in solid tumors at present, and has good clinical application value.

Provided herein are multifunctional molecules comprising T cell receptor variable beta-binding moieties and cytokines and methods of treating conditions or diseases in a subject using the same. Also provided herein is a combination therapy using the multifunctional molecules comprising T cell receptor variable beta-binding moieties and cytokines and an HDAC inhibitor.

The invention relates to the field of biological medicine, and provides an HDAC inhibitor coated liposome degradation agent, which comprises hydrogenated lecithin, cholesterol, an HDAC inhibitor, targeted EGFR drug modified functional phospholipid and E3 ligase ligand modified functional phospholipid. The invention further provides a preparation method of the liposome degradation agent wrapping the HDAC inhibitor and application of the liposome degradation agent in preparation of antitumor drugs. The EGFR-targeted liposome degradation agent is combined with the HDAC inhibitor, malignant proliferation of the osimertinib-resistant non-small cell lung cancer is synergistically overcome from multiple channels, and a new treatment thought is expected to be provided for clinical osimertinib-resistant lung cancer patients.

The invention relates to application of HDAC (histone deacetylase) inhibitor and Cathepsin B inhibitor combined medicine in lung cancer treatment, and belongs to the technical field of biological medicine. Research finds that histone deacetylase inhibitors (HDAC inhibitors, HDACIs) can promote invasion and migration of tumor cells by inducing epithelial-mesenchymal transition while inhibiting tumor growth, and side effects are generated. Therefore, in order to inhibit the side effect and enable the HDAC inhibitor to effectively exert the curative effect clinically, the invention provides a novel medicine combination mode, the HDAC inhibitor and the Cathepsin B inhibitor are combined for use, so that the antitumor activity of the HDAC inhibitor is retained, the tumor invasion and migration capability induced by the HDAC inhibitor is effectively inhibited, and the curative effect of the HDAC inhibitor is effectively exerted clinically. A new strategy is provided for precise treatment of solid tumors, and the method is verified in treatment of lung cancer.

This invention relates to agents, compositions, and methods for use in treating or ameliorating symptoms of cancer. Exemplary synergistic therapies include the use of antisense oligonucleotide agents for suppressing expression of TGF-β2 in combination with alkylating agents or HDAC inhibitors. Patients can be distinguished by reduced histone deacetylases. Additional therapies include the use of antisense oligonucleotide agents for suppressing expression of TGF-β2 for patients who have (a) low genomic methylation and / or (b) high TGF-β2 expression. Diagnostic information and methods are provided with histone deacetylases.

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.

The application discloses a pterostilbene paeonol chalcone amide derivative shown in a general formula (I) or a pharmaceutically acceptable salt thereof, the compound has a good inhibiting effect on human lung cancer cell A549, human hepatoma cell HepG2, colon cancer cell HCT116 and human osteosarcoma cell U-2OS tumor cell, and shows a certain inhibiting effect on HDAC1, 2, 3, 6 and 8, and has the potential of being used as an HDAC inhibitor type antitumor drug. The method for preparing the compound has the characteristics of easy availability of raw materials, simple operation and high yield.

The invention discloses application of an HDAC (histone deacetylase) inhibitor to improvement of in-vivo delivery of lipid nanoparticles, and belongs to the technical field of gene therapy. HDACi is a small molecule compound for inhibiting histone deacetylase (HDAC), and the gene expression is influenced by inhibiting the HDAC so as to improve the acetylation level of histone or other non-histone substrates. After an organism is treated by the HDAC inhibitor, the in-vivo delivery efficiency of the lipid nanoparticles can be improved by 62%, and the effectiveness and safety of the nucleic acid medicine based on the lipid nanoparticles are improved. Therefore, the method disclosed by the invention lays a solid foundation for gene therapy based on lipid nanoparticles.

The present invention relates to compound of Formula 1 for use in treating IPF, by reducing collagen deposition in lungs, attenuating the fibrotic marker's expression (in IPF cell-lines Bleomycin induced rat lungs) and improving the bleomycin induced pathological changes in rat lungs, and ARDS, by reducing the cytokine storm. The invention also relates to compound of Formula 1 for use in treating various fibrotic disorders like lung injuries caused by virus or bacterial infections, cardiac, hepatic and kidney fibrosis.

The invention discloses a culture medium, a method and a model for constructing polarized 3D human intestinal organoids, and relates to the field of organoid culture. The culture medium comprises the following components: 5 to 15 [mu] g / mL of Wnt3a, 30 to 100 [mu] g / mL of R-spondin-1, R-spondin-2 and / or R-spondin-3, 10 to 50 nmol of a gamma-secretase inhibitor, 2 to 10 [mu] mol of a Wnt agonist, 50 to 200 [mu] mol of an HDAC inhibitor, 0.5 to 2% of an N2 supplement, 1 to 4% of a B27 supplement, 5 to 20 [mu] g / mL of IGF-1, 0.1 to 2 [mu] mol of a TGF-beta receptor inhibitor, and the balance of a Williams E solution. The model obtained by the invention realizes long-term stable mature differentiation state and physiological polarity maintenance.