48 results about "HDAC1" patented technology

The invention relates to the field of a medical technology. The invention discloses a multi-targeted antitumor active evodiamine derivative with antitumor activity and preparation and application thereof. The general structural formula of the compound is as shown in A or B. In-vitro antitumor activity test of the compound shows strong in-vitro antitumor activity and broad spectrum antitumor characteristics. Top1, Top2 and HDAC1 inhibitory activity shows that most compounds have strong inhibiting effect on Top1, Top2 and HDAC1 and are Top1 / Top2 / HDAC1 three-target inhibitors. The compound of the invention can be used in treating malignant tumor and diseases related to differentiation and proliferation.

The invention relates to the treatment of mammalian diseases manifested by abnormal cell growth and / or abnormal cell proliferation. More particularly, the invention relates to the use of combination therapies to control abnormal cell growth and / or abnormal cell proliferation. In particular, the invention relates to the use of isotype-selective inhibitors of histone deacetylases 1, 2 and / or 3 (HDACs 1-3), as well as isotype-selective inhibitors of HDAC1 and / or HDAC2, to potentiate therapeutic activity of microtubule-stabilization agents.

This invention is based in part on the discovery that miR-34 is independent of p53. It has been discovered that miR-34 functions in a TP53 -independent tumor suppression pathway. Specifically, miR-34-induced inhibition of cancer cell growth was found to be the same in p53-normal and p53-deficient cells. Thus, miR-34 has a more central role during tumor suppression that is uncoupled from p53. In the absence of p53, miR-34, unlike certain other miRNAs, is sufficient to induce an up-regulation of genes known to be regulated by p53, including but not limited to p21<CIP1 / WAF1>(CDKN1A), PUMA, BAX, NOXA, PHLDA3, and MDM2 and a down-regulation of HDAC1. Therefore, these biomarkers can be used as biomarkers of miR-34 activity. The invention is further based on the discovery that some of these biomarkers are indispensable for a therapeutic response to miR-34 activity, and are thus prerequisite biomarkers of miR-34 activity.

The invention discloses cyclic peptide compounds adopting a chemical structure shown in the general formula I or pharmaceutically acceptable salt, isomers, racemes, pro-drugs or solvates of the cyclic peptide compounds. Compared with a positive control (SAHA), the compounds have remarkable activity for inhibiting deacetylation of HDAC enzymes (mainly include HDAC1, HDAC2, HDAC3, HDAC8 and HDAC11) closely related with tumor proliferation and metastasis as well as remarkable activity for inhibiting tumor cell growth.

A method for treating cancer is described using combination therapies comprising the use of hyperbaric oxygen with histone deacetylase inhibitors, with and without glycolytic therapies. The patient is subjected to a hyperbaric environment of substantially pure oxygen. A predetermined dose of one or more HDACI substances is administered to the patient. In addition, glycolitic inhibitors may also be administered. Dosages, pressures, and durations are selected as described herein to have a therapeutic effect on the patient.

The present invention relates to novel heteroaryl amide derivatives of formula (I), as selective inhibitors of histone deacetylase 1 and 2 (hdac1-2), to methods for the production of same, to pharmaceutical compositions comprising these compounds, and to the use of said compounds for the production of a medicament for the treatment of pathological conditions or diseases that can be improved by means of the inhibition of the activity of histone deacetylase class I, particularly HDAC1 and HDAC2, such as cancer, neurodegenerative diseases, infectious diseases, inflammatory diseases, heart failureand cardiac hypertrophy, diabetes, polycystic kidney disease, sickle cell disease and beta-thalassemia disease, and to methods for the treatment of the diseases mentioned above.

The invention discloses a saussurea-obvallata effective part and a preparing method and application thereof, and belongs to the technical field of plant extract. The saussurea-obvallata effective part is selected from the mixture of any mass ratio of one or two above of a saussurea-obvallata petroleum ether part, a saussurea-obvallata ethyl acetate part, a saussurea-obvallata n-butyl alcohol part and a saussurea-obvallata aqueous phase extraction part. The preparing method includes the steps that saussurea-obvallata whole plant is smashed, an ethanol solution with the mass percent concentration of 65% to 95% is added and subjected to reflux extraction, the obtained extracted liquid is concentrated and dried, and extract is obtained; the extract is dispersed in distilled water, extract dispersion liquid is obtained, petroleum ether, ethyl acetate and n-butyl alcohol are sequentially used as a solvent to extract the extract dispersion liquid, and after the solvent is volatilized, the saussurea-obvallata petroleum ether part, the saussurea-obvallata ethyl acetate part and the saussurea-obvallata n-butyl alcohol part are obtained; the extracted extract dispersion liquid is concentrated and dried, and the saussurea-obvallata aqueous phase extraction part is obtained. The saussurea-obvallata effective part has an application to preparing medicine for inhibiting a HDAC1 enzyme, and can be used for preparing antitumor medicine.

The invention relates to the technical field of drugs, in particular to a biomarker for COPD and application of the biomarker, and provides a COPD early diagnosis drug marker and a diagnostic drug kitcontaining the marker. The marker is eight senescence-related genes differentially expressed in the COPD: one or any combination of FOXO3, TP53, TGF<beta>1, HDAC1, NUF2, ATG3, AREG and E2F1, or one or any combination of 13 methylation loci of the senescence-related genes differentially expressed in the COPD. The degree of methylation of the marker in a control group and a COPD group is statistically significant (P<0.05), and the marker can be used as the biomarker in the diagnosis of the clinical COPD.

The invention provides a histone histone deacetylase inhibitor and application thereof. Specifically, the invention provides a compound of formula (I) as shown in the specification, and a pharmaceutically acceptable salt of the compound, and in the formula, the groups are defined as shown in the specification. The invention further provides a preparation method of the compound. The compound of formula (I), which is provided by the invention, can be adopted to treat a series of diseases mediated by histone histone deacetylases by inhibiting histone histone deacetylases (HDACs), particularly type-I histone histone deacetylases (subtypes such as HDAC1 and HDAC3), particularly including tumor diseases such as solid tumor and leukemia, neurodegenerative diseases, and the like.

The present invention provides three-dimensional structural information from the hyperthermophilic bacterium Aquifex aeolicus which is a histone deacetylase-like protein (HDLP). HDLP shares 35.2% amino acid sequence identity with human histone deacetylase (HDAC1). The present invention further provides three-dimensional structural information of HDLP bound by inhibitor molecules. The three-dimensional structural information of the present invention is useful to design, isolate and screen deacetylase inhibitor compounds capable of inhibiting HDLP, HDAC family members and HDLP-related molecules. The invention also relates to nucleic acids encoding a mutant HDLP which facilitates the determination of the three-dimensional structure of HDLP in the presence of a zinc atom.

A method of increasing the expansion and / or differentiation of a hematopoietic stem cell (HSC) comprising: (a) increasing the level and / or activity of a polypeptide encoded by at least one gene selected from trim27, xbp1, sox4, smarcc1, sfpi1, fos, hmgb1, hnrpdl, vps72, tcfec, klf10, zfp472, ap2a2, gpsm2, gpx3, erdr1, tmod1, cnbp1, prdm16, hdac1, pml and ski, or a functional variant of said polypeptide, in said cell; (b) increasing the level of a nucleic acid encoding the polypeptide or functional variant of (a) in said cell; or (c) any combination of (a) and (b).

The invention relates to an RT-PCR kit and a method for evaluating the concurrent intestinal cancer susceptibility of a hyperglycemia population by using the kit, belonging to the technical field of real-time fluorescence quantitative reverse transcription polymerase chain reaction kit development and human pathology combination. RT-PCR primers for detecting the transcriptional level of HDAC1 mRNA in serum include a primer F: 5'-GCTCCACATCAGTCCTTCC-3' and a primer R: 5'-GGTCGTCTTCGTCCTCATC-3'. The invention establishes a method for detecting HDAC1 mRNA in peripheral vein serum by using the specific primers; and a quantitative PCR amplification technology is adopted in the method, so that the sensitivity for detecting HDAC1 mRNA is greatly improved, and enough information can be obtained in extremely few specimens.

Provided herein are compounds and methods for inhibiting histone deacetylase ("HDAC") enzymes (e.g., HDAC1, HDAC2, and HDAC3).

A method for treating cancer is described using combination therapies comprising the use of hyperbaric oxygen with histone deacetylase inhibitors, with and without glycolytic therapies. The patient is subjected to a hyperbaric environment of substantially pure oxygen. A predetermined dose of one or more HDACI substances is administered to the patient. In addition, glycolitic inhibitors may also be administered. Dosages, pressures, and durations are selected as described herein to have a therapeutic effect on the patient.

The invention relates to a 2-aryl-4-(1H-pyrazol-3-yl)pyridine LSD1 / HDAC double-target inhibitor and a preparation method thereof, and application of the 2-aryl-4-(1H-pyrazol-3-yl)pyridine LSD1 / HDAC double-target inhibitor in preparation of antitumor drugs, belonging to the technical field of medicinal chemistry. The inhibitor has a general formula as described in the specification. In the general formula, R1 is preferably selected from CH3, OCH3 and H; and R2 is preferably F and H. The inhibitor disclosed by the invention has relatively strong inhibitory activity on both LSD1 and HDAC, and the IC50 value of the inhibitor on HDAC1 is less than 5 nM, and the inhibitor is remarkably superior to a positive drug SAHA. The LSD1 / HDAC double-target inhibitor has good in-vitro anti-tumor activity on human acute myelogenous leukemia THP-1 cell strains, is superior to a positive drug SAHA, provides a basis for research and development of LSD1 / HDAC double-target inhibitor drugs, and can be used as a candidate or a lead compound for further development for development of anti-tumor treatment drugs.

The invention discloses a double-target inhibitor as well as a preparation method and application thereof. The double-target inhibitor has a structure shown as a formula (I), wherein R1 is H, an electron-withdrawing group or an electron-donating group; R is alkyl; n is equal to 1 to 5. The double-target inhibitor provided by the invention can be used for selectively inhibiting HDAC6 and IC50 values on HDAC1 and HDAC8 are greater than 20 muM; the double-target inhibitor is used as a prodrug to be subjected to hydrolysis reaction in cells, and tubulin and an HDAC double-target inhibitor can be released; the inhibition activity of histone deacetylase on solid tumors is improved; the double-target inhibitor has a relatively good inhibition effect on tumor cells. The formula (I) is shown in thedescription.

Provided herein are compounds and methods for inhibiting histone deacetylase ("HDAC") enzymes (e.g., HDAC1, HDAC2, and HDAC3).

The invention discloses a corydalis pygmaea effective part, as well as a preparation method and application thereof, and belongs to the technical field of a plant extract. The corydalis pygmaea effective part is mixture of one or more than one of a corydalis pygmaea petroleum ether part, a corydalis pygmaea ethyl acetate part and a corydalis pygmaea aqueous extraction part in an arbitrary mass ratio. The preparation method comprises the following steps: grinding whole grass of corydalis pygmaea, refluxing and extracting with an ethanol solution having a volume percentage concentration of 65-95 percent, concentrating and drying the extract to obtain an extract; dispersing the extract with distilled water to obtain an extract dispersant, extracting the extract dispersant sequentially with petroleum ether, ethyl acetate and n-butyl alcohol, and volatizing solvent to obtain a corydalis pygmaea petroleum ether part and a corydalis pygmaea ethyl acetate part; and concentrating and drying the extracted extract dispersant to obtain a corydalis pygmaea water-phase extraction part. The corydalis pygmaea effective part can be applied to preparation of medicines for inhibiting HDAC1 enzyme, and can be used for preparing anti-tumor medicines.

The present invention provides three-dimensional structural information from the hyperthermophilic bacterium Aquifex aeolicus which is a histone deacetylase-like protein (HDLP). HDLP shares 35.2% amino acid sequence identity with human histone deacetylase (HDAC1). The present invention further provides three-dimensional structural information of HDLP bound by inhibitor molecules. The three-dimensional structural information of the present invention is useful to design, isolate and screen deacetylase inhibitor compounds capable of inhibiting HDLP, HDAC family members and HDLP-related molecules. The invention also relates to nucleic acids encoding a mutant HDLP which facilitates the determination of the three-dimensional structure of HDLP in the presence of a zinc atom.

The invention relates to a 2-aryl isonicotinic acid amide LSD1 / HDAC double-target inhibitor and a preparation method thereof, and application of the 2-aryl isonicotinic acid amide LSD1 / HDAC double-target inhibitor in preparation of antitumor drugs, belonging to the technical field of medicinal chemistry. The inhibitor has a general formula as described in the specification. In the general formula, R1 is preferably selected from OH and H; R2 is preferably selected from OH, OCH3, F, H and CH3; R3 is preferably selected from H, OH, Cl, OCH3 and NH2; R4 is preferably selected from H, OH, CF3, OCH3 and CH3; and X is N or CH. The inhibitor provided by the invention has relatively strong inhibitory activity on LSD1 and HDAC1, provides a basis for research and development of LSD1 / HDAC double-target inhibitor drugs, and can be used as a further candidate or lead compound for developing antitumor therapeutic drugs.

This invention relates to generally inhibiting histone deacetylase (“HDAC”) enzymes (e.g., HDAC1, HDAC2, and HDAC3).

The invention discloses a composition for detecting chemoradiotherapy sensitivity of rectal cancers, a micro array and a computer system. The composition of the invention includes oligonucleotides that are specifically bound to a part of contiguous regions of a gene selected from a group consisting of ABL1, AR, CDK1, HDAC1, IRF1, JUN, PRKCB, RELA-3, STAT1-2, SUMO1-3, ACTB, CSNK1G2, FARP1, GAPDH, and RPLP0. The composition can be used to detect the relative expression level of each gene. In addition, based on expression level differences, and a sensitivity index (RSI) is obtained via a specificalgorithm, and can be used to effectively determine the chemotherapy sensitivity of a detection sample.

The invention provides a histone deacetylase inhibitor and use thereof. Specifically, the present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein the definitions of each group are as described in the specification. The present invention also provides a preparation method of such compounds. The compounds of formula (I) of the present invention can be used for the treatment of histone deacetylases (HDACs) by inhibiting histone deacetylases (HDACs), especially class I histone deacetylases (subtypes such as HDAC1, HDAC3, etc.). A series of diseases mediated, including the treatment of solid tumors, leukemia and other tumor diseases, and neurodegenerative diseases.

The invention relates to an HDAC6 selective inhibitor, and belongs to the technical field of medicine. The to-be-achieved technical purpose is to provide the novel HDAC6 selective inhibitor. The HDAC6selective inhibitor comprises a compound shown in a formula I and a pharmaceutically acceptable auxiliary material. It is found for the first time that the compound shown in the formula I can inhibitHDAC6 while having a small inhibitory effect on HDAC1 and HDAC10, therefore, the HDAC6 selective inhibitor can be prepared, the inhibition rate of the HDAC6 selective inhibitor is high, and a new choice is provided for the HDAC6 inhibitor.

The invention discloses a dihydroindene amine derivative as well as a preparation method and application thereof. The invention provides a dihydroindene amine compound as shown in a formula I or a pharmaceutically acceptable salt thereof. The compound provided by the invention has good inhibitory activity on HDAC6, has good selectivity on HDAC1 and / or HDAC3, and has good metabolic stability.

The invention relates to a 5-aryl nicotinamide LSD1 / HDAC double-target inhibitor and a preparation method and application thereof in preparation of antitumor drugs, and belongs to the technical field of medicinal chemistry. The compound has the following general formula shown in the specification, wherein R1 is preferably OH, CH3 and H; and R2 is preferably OH, OCH3, F, CN, H and CH3. The compound has relatively strong inhibitory activity to LSD1 and HDAC1, and the IC50 of most compounds to HDAC1 is less than 10 nM, which is superior to that of a positive drug SAHA. The in-vitro anti-tumor activity IC50 of a plurality of compounds on a human colon cancer HCT-116 cell strain, a human gastric cancer MGC-803 cell strain and human leukemia THP-1, MOLT-4 and MV4: 11 cell strains is less than 1.0 mu M, and the in-vitro anti-tumor activity of the compound I-4 on THP-1 is 6 times that of SAHA. The compound provides a basis for research and development of LSD1 / HDAC double-target inhibitor drugs.