87 results about "Histone Demethylases" patented technology

The present application discloses compounds capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament. The compounds take the form

Tranylcypromine derivatives useful as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of histone demethylases LSD1 and LSD2, such as the diseases characterized by deregulation of gene transcription, cell differentiation and proliferation, e.g. tumors, viral infections, are herein described. These compounds belong to the structural formula (I) wherein A and R₃ are as defined in the specification. The invention also relates to the preparation of these compounds, as well as to compositions containing them and to therapeutic use thereof.

Provided are a novel compound, preparing method thereof, and use thereof as inhibitor of histone demethylase. The compound represented by Chemical Formula 1 has activity which inhibits histone demethylase and thus is capable of specifically and effectively inhibit activity of histone demethylase.

Disclosed are compounds and pharmaceutical compositions containing compounds that inhibit JMJD2 proteins, including those of the formula (I):

wherein R¹, R², R³, R⁴, and R⁵ are as defined herein or pharmaceutically acceptable salts thereof. Also disclosed is a method of preventing or treating a viral infection of a host, comprising administering to the host an effective amount of an inhibitor of the JMJD2 family of histone demethylases, for example, a compound of the formula (I). The viral infection may be a primary infection, reactivation of a virus after latency in a host, or may be in a mammal that has undergone, is undergoing, or will undergo immunosuppressive therapy.

The present invention relates to compounds formula (I):

and to salts thereof, wherein R¹-R⁴ and A have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of histone demethylases, such as KDM5. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.

The invention belongs to the technical field of plant gene engineering, and more particularly relates to a paddy rice histone demethyl methylase gene, coded protein and the application thereof. The invention provides a new paddy rice histone demethyl methylase gene OsJMJ706, due to inactivation, heteroplasia of rice flowerthe, heteroplasia or deficit of internal and external glumes, as well as lessening of seeds can be caused on the gene, and by being detected by the method of western blot, the gene is proved to have enzyme activity for removing histone H3K9me3 and H3K9me2 locus methylate. The invention provides nucleic acid sequence and protein sequence of the gene as well as the application thereof.

LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.

In one aspect, the invention relates to substituted (E)-N'-(1- phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The invention discloses a small-molecular compound/combination for preventing, delaying or reversing the aging of cells, tissues, organs and bodies, a product thereof, and a use of the compound/combination and the product. The small-molecular compound/combination includes at least one of a DNMT inhibitor, an HMT inhibitor, a histone demethylase inhibitor, a TGF-beta inhibitor, a WNT/beta-catenin agonist, a cAMP agonist, a lysine deacetylase inhibitor, an RAR agonist and an ROCK inhibitor. The small-molecular compound or the combination thereof is adopted to prevent, delay or reverse the agingof cells, tissues, organs and bodies and prolong the telomere length of the cells, and has the advantages of clear action target, clear, mature and stable composition, and accuracy in regulation of the anti-aging process; and the quality control and the large-scale production of the small-molecular compound are easy. The bodies or cells do not express dry genes in the action process, so the safetyis high; and the small-molecular compound and the combination thereof can be easily absorbed by the bodies, can prevent, delay and reverse the aging at the overall level of cells, tissues, organs andbodies, and is of great significance to delaying the process of human aging and improving the health state and the life quality.

The invention provides a histone demethylase LSD1 (lysine specific demethylase 1) inhibitor. The invention relates to piperazine-containing compounds and pharmacologically acceptable salts thereof and use of the piperazine-containing compounds and pharmacologically acceptable salts thereof as the LSD1 inhibitor; the general structural formula of the piperazine-containing compounds is described in the description. The invention belongs to the field of pharmaceutical chemistry. An in-vitro LSD1 activity inhibition test proves that the piperazine-containing compounds implemented by the invention have an obvious inhibiting effect for LSD1 activity, thus being used as active ingredients for preparing LSD1 inhibitor medicines.

Provided are a pharmaceutical composition with a synergistic anti-osteosarcoma effect and application thereof. The invention discloses the pharmaceutical composition containing a VEGFR2 selective inhibitor Apatinib and a histone demethylase inhibitor GSK-J4 and the application thereof. Apatinib and GSK-J4 are used in combination to achieve the synergistic anti-osteosarcoma effect, the osteosarcomacell growth can be obviously inhibited, and the pharmaceutical composition is used for treatment of tumors like osteosarcoma.

The invention discloses an application of histone demethylase KDM5C (lysine(K) demethylase 5C) in screening of drugs for treating the fatty liver and related diseases of the fatty liver. A human normal hepatocyte L02 cell line, an L02 cell line with overexpressed histone demethylase KDM5C and an L02 cell line with KDM5C (CRISPR-Cas9) knockout are adopted as experimental subjects, and the functionof the gene KDM5C is studied by a fatty liver cell model induced by palmitic acid and oleic acid jointly. Studies show that the accumulation of lipid in L02 cells induced by PA and OA is significantlyincreased during overexpression of KDM5C; the accumulation of lipid in the L02 cells induced by PA and OA is significantly decreased when expression of KDM5C is decreased, that is, expression of thegene KDM5C can promote generation and development of the fatty liver and related diseases. Based on the function of KDM5C in deterioration of the fatty liver, a target for development of drugs for prevention, alleviation and/or treatment of the fatty liver and related diseases is provided.

The invention discloses a histone demethylase gene JMJ703 for regulating a rice stem height, and applications thereof. According to the present invention, one of histone demethylases and gene JMJ703 thereof are selected through searching in a chromatin protein database, wherein the full-length cDNA accession number is AK121381, a gene ID number is 4338043, a prediction coding region comprises 3717 bp, and 1238 amino acids are coded; a RNA interference vector of the gene is transformed into rice through a RNA interference method, and results show that a stem height of the transgenic plant is shorter than a stem height of the wild type while a length of the leaf has no apparent change so as to improve a column shape of the rice; tobacco heterogenesis in vivo test results show that JMJ703 protein is demethylase of histone H3K4me1/H3K4me2/H3K4me3; and the JMJ703 is functional histone demethylase gene and can be provided for regulating a stem elongation process of the rice, wherein the stem of the rice expressed after gene inhibition becomes short and a characteristic of lodging resistance is provided while developments of leaves and other organs are normal so as to provide a selective plant type for breeding.

The invention relates to applications of a transcription factor CREB in JHDM2A gene expression regulation and pig lipid deposition reduction. By overexpression of CREB in pigs, or by improvement of the CREB phosphorylation level in pigs, or by promotion of combination of pig CBP protein and the phosphorylated CREB, JHDM2A gene expression in pigs is up-regulated, thus regulating lipid metabolism pathways from the epigenetics and reducing pig lipid deposition. Novel applications of the transcription factor CREB in the epigenetics are provided for the first time and the transcription factor CREB can be used for reducing pig lipid deposition, namely, expression of the histone demethylase JHDM2a is directly activated so that the histone demethylase JHDM2a can regulate the lipid metabolism pathways from the epigenetics, thus minifying lipid cells and increasing the meat factor. A novel candidate gene is provided for genetic breeding, meat quality improvement, and the like in the animal husbandry.

The present invention relates to methods for treatment or prevention of autoimmune and inflammatory diseases and conditions by inhibiting or modifying histone demethylation. In a further aspect the invention relates to a method for identifying agents useful in said methods of treatment. The invention particularly describes the role of certain histone demethylase enzymes in these diseases and conditions and their use as therapeutic and screening targets.

The invention discloses a target regulation system for dedifferentiation of somatic cells, a kit and an application of the kit. The target regulation system regulates the somatic cells: inhibition ofPKC activity, inhibition of DNMT activity and/or inhibition of HMT activity and/or inhibition of the activity of histone demethylase; corresponding regulation key targets include PKC, DNMT and/or HMTand/or histone demethylase; the somatic cells are differentiated cells. The target regulation system provided by the invention can promote the efficiency of adopting small molecules to induce the somatic cells to transdifferentiate into different types of functional target cells, and has the advantages of clear targets, clear ingredients, maturity and stability, and easy quality control and large-scale production.

Substituted (E)-N-(1-phenylethylidene)benzohydrazide analogs or (3-(5-chloro-2-hydroxyphenyl)-4-METHYL-1 H-pyrazol-1-YL)(3- (morpholinosulfonyl)phenyl)methanone, derivatives thereof, and related compounds are useful as inhibitors of lysine-specific histone demethylase, including LSD1. Synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1 (lysine-specific demethylase). A pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, and one or more of: (a) at least one agent known to increase histone demethylase activity; (b) at least one agent known to decrease histone demethylase activity; (c) at least one agent known to treat a disorder of uncontrolled cellular proliferation; (d) at least one agent known to treat a neurodegenerative disorder; (e) instructions for treating a neurodegenerative disorder; or (f) instructions for treating a disorder associated with uncontrolled cellular proliferation.

The invention relates to a 5-benzylidene-2-phenyl thiazolone compound as well as preparation and application thereof. In particular, the compound provided by the invention has a structure shown as a general formula (I), wherein the definitions of each group and substituent are described in the description. The invention further discloses a preparation method of the compound and application of thecompound to the prevention and/or treatment of cancer-related diseases. The compound provided by the invention has superior inhibitory activity on protein-arginine methyltransferases 1 (PRMT1), protein-arginine methyltransferases 5 (PRMT5) and histone demethylase LSD1, and can induce tumor cell apoptosis and retard tumor cells at a G1 stage, so that the compound can be used for preparing a seriesof medicaments for treating diseases related to abnormal activities of the PRMT1, the PRMT5 and the histone demethylase LSD1. The general formula (I) is shown in the description.