115 results about "HDAC inhibitor" patented technology

The invention belongs to the field of biological medicine, and relates to application of an HDAC (histone deacetylase) inhibitor in treatment of liver cancer, in particular to application of the HDAC inhibitor in preparation of medicines for treating liver cancer, slowing down liver cancer progress and / or preventing liver cancer recurrence, a medicine composition for treating liver cancer, slowing down liver cancer progress and / or preventing liver cancer recurrence and a treatment method.

The invention provides an application of a histone deacetylase (HDAC) inhibitor and / or a JAK2 inhibitor in inducing hematopoietic stem progenitor cells, mononuclear cells or total nucleated cells to generate megakaryocytes and / or megakaryocyte progenitor cells. The invention also provides methods of inducing hematopoietic stem progenitor cells, mononuclear cells or total nucleated cells to produce megakaryocytes and / or megakaryocyte progenitor cells comprising exposing the cells to an HDAC inhibitor, and / or exposing the cells to a JAK2 inhibitor.

The present invention belongs to the technical field of medicines. The present invention relates to an imidazolidinedione HDAC inhibitor, and a preparation method therefor and the use thereof. Provided in the present invention is an imidazolidinedione HDAC inhibitor, which inhibitor is a substituted imidazolidinedione compound as represented by general formula V, or a stereoisomer, a hydrate or a pharmaceutically acceptable salt thereof. The inhibitor has efficient and good HDAC enzyme inhibitory activity, and also has good in-vitro anti-tumor activity. The inhibitor provides a new way for the application of an HDAC inhibitor in tumors / or the treatment of diseases related to uncontrolled histone deacetylase activity.

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 disclosure, in one aspect, relates to methods for treating cancer in a subject, the methods including at least the steps of administering at least one drug from each of at least two classes selected from an inhibitor of poly-ADP ribose polymerase (PARP inhibitor), an inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs inhibitor), an inhibitor of wild-type isocitrate dehydrogenase (IDH inhibitor), an inhibitor of histone acetyltransferase (HAT inhibitor), an inhibitor of histone deacetylase (HDAC inhibitor), an inhibitor of DNA polymerase Θ (POLΘ inhibitor), an inhibitor of platelet-derived growth factor receptor (PDGFR inhibitor), and a DNA alkylating agent to the subject. In any of these aspects, the disclosed method allows for administering lower doses of the drugs in combination compared to administration as single drugs while preventing the recurrence of the cancer, preventing drug resistance of the cancer, and reducing side effects associated with cancer treatment.

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.

Provided is a method of differentiating human pluripotent stem cells (hPSCs) into mature pancreatic β cells, comprising contacting hPSC-derived, differentiated immature pancreatic β cells with a histone deacetylase (HDAC) inhibitor.

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 present invention relates to a method for killing cancer cells using a combination of an HDAC inhibitor and an anti-PD-1 antibody or an anti-PD-L1 antibody. The present invention can effectively affect the following aspects: prolonging the survival of animals suffering from cancer, tumors, tumor-related diseases and tumor diseases; inhibiting the growth of tumor-related proliferating cells; or tumor degeneration.

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 invention discloses a class of CXCR4 / HDAC dual inhibitors, their preparation methods, and applications. These dual CXCR4 / HDAC inhibitors are compounds having the structures represented by formula (I) or (II) and / or pharmaceutically acceptable salts thereof: #imgabs0# In formulas (I) and (II): R1 is selected from #imgabs1, R2 is selected from #imgabs2, and L is empty or a saturated or unsaturated aliphatic hydrocarbon chain with a C1-C6 range, preferably a C1-C4 range. These dual CXCR4 / HDAC inhibitors exhibit both CXCR4 antagonism and HDAC inhibition, and are multi-target derivatives that can synergistically achieve anti-tumor, anti-inflammatory, and anti-depressant effects.

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.

A switch to haploid embryogenesis is controlled by the activity of histone deacetylases (HDACs). Blocking HDAC activity with HDAC inhibitors (HDACi), e.g., trichostatin A (TSA), in Brassica napus, B. rapa, Arabidopsis thaliana, and Capsicum annuum male gametophytes leads to a large increase in the proportion of cells that undergo embryogenic growth. In B. napus, treatment with one specific HDACi (SAHA) improves the conversion (i.e., germination) of these embryos into seedlings. Existing methods of culturing microspores of angiosperm plants following stress to produce haploid embryos, haploid plants, and double haploid plants can be improved by adding HDACi to the culture medium. Advantageously, species hitherto recalcitrant to haploid embryogenesis via microspore culture are rendered useful when using HDACi. Haploid and double haploid plants are of industrial application in the plant breeding programmes.