63 results about "EZH2" patented technology

Disclosed are methods of increasing R0R1 in a cell comprising administering an EZH2 inhibitor, G9A inhibitor, DNMT1 inhibitor or combination thereof to the cell. Disclosed are methods of treating lymphoma in a subject comprising administering to the subject one or more EZH2 inhibitors, G9A inhibitors, DNMT1 inhibitors or combinations thereof, wherein the one or more EZH2 inhibitors, G9A inhibitors, DNMT1 inhibitors or combinations thereof increase expression of R0R1 in one or more B cells in the subject; and one or more R0R1 targeting therapeutics.

The present invention provides SETD2 protein inhibitors, as well as methods, compositions and kits for treating a disease, disorder or condition in a subject using a SETD2 protein inhibitor and optionally a second therapeutic agent, wherein the second therapeutic agent comprises one or more glycocortin receptor agonists, one or more immunomodulatory drugs, one or more proteasome inhibitors, one or more Bcl-2 inhibitors, one or more multi-effect pathway modulators, one or more XPO1 inhibitors, and one or more pharmaceutically acceptable salts thereof, one or more histone deacetylase inhibitors or one or more EZH2 inhibitors, or a combination thereof.

GD2 specific chimeric antigen receptor effector cells for the treatment of solid tumors, possibly in combination with an enhancer of a Zeste homolog 2 (EZH2) inhibitor. The invention relates to a GD2-specific chimeric antigen receptor (GD2. CAR) effector cell for use in the treatment of solid tumors, in particular in the treatment of extracranial GD2 + tumors, such as soft tissue sarcoma and osteosarcoma, neuroblastoma, melanoma, lung cancer, bladder cancer and retinoblastoma, and brain tumors. In addition, the present invention also relates to the use of the GD2. CAR genetically modified effector cell in combination with an enhancer of a Zeste homolog 2 (EZH2) inhibitor for the treatment of solid tumors.

The invention belongs to the technical field of disease model construction, and particularly relates to a construction method of a chronic myelogenous leukemia mouse model with conditional human EZH2 overexpression and RUNX1 knockout. According to the invention, a chronic myelogenous leukemia mouse transgenic mouse model with conditional human EZH2 overexpression and RUNX1 knockout is successfully constructed, the model is induced to be converted from a chronic stage to a sudden change stage, and particularly, the model is a transgenic mouse model which is positive in Lyz2-CreERT2 / EZH2 / RUNX1 and carries BCR-ABL and SCL-tTA. It is proved that a human EZH2 conditional overexpression and RUNX1 knockout chronic myelogenous leukemia mouse transgenic mouse model has feasibility and importance for research on conversion from CML CP to BC samples, and a molecular mechanism for conversion from chronic myelogenous leukemia to a sudden change stage is revealed for research. And a new animal model and a new research idea are provided for understanding of disease progression and development of a new treatment strategy.

The present invention relates to pharmaceutical compositions comprising inhibitor(s) of human histone methyltransferase EZH2, and methods of cancer therapy using the EZH2 inhibitor(s).

The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.

To provide methods for treating diseases or disorders responsive to inhibition of EZH2.SOLUTION: The present disclosure relates to a crystalline form 1 of 7-chloro-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-2,4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide, which is useful as a modulator for the activity of histone methyl modifying enzymes.SELECTED DRAWING: None

Provided herein is (R)-7-chloro-2-((1r,4R)-4-(3-methoxyaetidin-1-yl)cyclohexyl)-2,4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide, or a pharmaceutically acceptable salt thereof for use in methods of treating certain cancers having at least one BAP1 mutation.

Disclosed are substituted pyrrolidones and piperidones which may be utilized as EZH2 targeting agents. The substituted pyrrolidones and piperidones may include substituted 2-pyrrolidones and 2-piperidones. The disclosed pyrrolidones and piperidones may be used in pharmaceutical compositions and methods for treating cell proliferative disorders such as cancer.

The invention relates to the technical field of biomedicine, in particular to a marker for risk assessment of vitreous retinal lymphoma and application of the marker. The marker comprises mutation sites of vitreoretinal lymphoma related genes, and the vitreoretinal lymphoma related genes comprise BTG1, BTG2, DMD, HLA-A, LRP1B, PTPN11, PTPRD, STAT5A, TGFBR2, VHL, ARID1A, ARID1B, ATM, BCL2, BCL6, BCOR, BRAF, CARD11, CD79A, CD79B, CDKN2A, CDKN2B, EP300, ETV6, EZH2, GNA13, IRF4, JAK1, JAK2, JAK3, KMT2D, MYC, MYD88, NOTCH1, NOTCH2, PIK3CA, PIM1, PRDM1, according to the application, the markers are screened out, a corresponding detection object is designed based on the screened markers, and a vitreous retinal lymphoma risk assessment method with high sensitivity and reliability and a corresponding risk assessment product are constructed. According to the method, an accurate risk judgment result can be obtained based on a comprehensive score of VRL related somatic cell gene mutation in a to-be-detected sample.

Provided herein are (R)-7-chloro-2-((1r, 4R)-4-(3-methoxyazetidin-1-yl) cyclohexyl)-2, 4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1, 2-dihydropyridin-3-yl) methyl) benzo [d] [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 3] dioxol-5-carboxamide or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof.

The invention provides application of histone methyltransferase EZH2 as a therapeutic target of diabetic nephropathy podocyte senescence and injury, and relates to the technical field of biological medicine. It is found that the expression level of EZH2 in podocyte under the high glucose condition is remarkably increased, and conditions are provided for taking EZH2 as a biomarker for diagnosing or evaluating diabetic nephropathy podocyte damage and senescence. Subsequently, it is verified that podocyte damage of db / db mice can be remarkably improved, proteinuria of the db / db mice can be reduced, pathological damage of kidneys can be relieved, glomerular senescence of the db / db mice can be delayed, damage and senescence of podocytes under the high-glucose condition can be remarkably improved, the purpose of protecting the kidneys is achieved, the development of diabetic nephropathy is delayed, and the development of diabetic nephropathy is delayed. Therefore, the EZH2 can be used as a potential target for treating diabetic nephropathy.

The present application provides a compound represented by formula (I), or a pharmaceutically acceptable salt, ester, prodrug, complex, solvate, hydrate, or isomer thereof; and a use thereof in preparing drugs used to treat EZH2-mediated disease.

Provided here are methods of treating lymphomas for example, peripheral T-cell lymphomas (PTCLs) (e.g., nodal Tfh cell lymphomas) and / or cutaneous T-cell lymphomas (CTCLs) in a subject, by administering to the subject Compound A, or a pharmaceutically acceptable salt thereof. In some cases, the lymphomas are BCL6 positive. In some cases, the lymphomas are relapsed or refractory. In some cases, the subjects are treatment-naïve (i.e., previously untreated).

The invention provides a liver cancer prognosis evaluation method, system and equipment, a medium and a program product, and relates to the field of intelligent medical treatment. The invention discloses heterogeneity of liver cancer cell subpopulations, in particular characteristics and molecular mechanisms of MVI-related cell subpopulations (such as Hep-C4); a specific cell subset related to poor prognosis of a liver cancer patient is identified, the effect of the specific cell subset in tumor growth and metastasis is explored, metabolic reprogramming of liver cancer cells, particularly the effect of a methionine metabolic pathway in promotion of tumor cell invasion and metastasis, is researched, and a theoretical basis is provided for metabolic intervention of liver cancer. Potential molecular markers (such as a combined marker of STMN1 and EZH2) are identified and used for prognosis evaluation and treatment response monitoring of liver cancer patients, and personalized medical treatment and precise treatment can be achieved.

The present application relates to the treatment of asthma by an inhibitor specific for EZH2, preferably GSK343.

Provided are novel antisense oligonucleotides that promote exon 14 skipping in the EZH2 gene, and their use in the treatment of cancer and other diseases.

The present invention provides a benzoxazole small molecule compound, which is an inhibitor of the Zeste gene enhancer homolog 2 (EZH2) and can be used to prevent and / or treat EZH2-mediated related diseases, such as malignant tumors.

This invention relates to methods for treating cancer, providing methods for treating solid tumors, B-cell lymphomas, or cancers with abnormal H3-K27 methylation, the method comprising orally administering a dosage form of EPZ-6438 in a therapeutically effective amount to a subject in need. This invention also relates to pharmaceutical compositions comprising one or more inhibitors of the human histone methyltransferase EZH2, and methods for treating cancer using such one or more EZH2 inhibitors.

The present invention relates to a preparation method for an amide compound and an application thereof in the field of medicine. Specifically, provided by the present invention is an amide small molecule compound which is an inhibitor of Zeste gene enhancer homolog 2 (EZH2) and which may be used to prevent and / or treat EZH2-mediated related diseases, comprising tumors, myeloproliferative diseases or autoimmune diseases.

Described herein is a EZH2 antisense oligonucleotide (ASO) epigenetic modulator of fragile X messenger ribonucleoprotein 1 (FMRI), its pharmaceutical compositions, and methods of treating a fragile X-associated disorder with the enhancer of zeste homolog 2 (EZH2) ASO. Also includes are pharmaceutical compositions including the EZH2 ASO and an ASO that decreases splicing between Exons 1 and 2 of FMR1-217. Methods of treating a fragile X-associated disorder with an EZH2 ASO and an ASO that decreases splicing between Exons 1 and 2 of FMR1-2F7 are also described.

The invention discloses a novel application of squamocin, and finds that the squamocin can effectively degrade histone methyltransferase EZH2 and MYC in head and neck squamous cell carcinoma (HNSCC), stomach cancer (GC) and colorectal cancer (CRC) cells and inhibit the cancer promoting transcriptional activity of the MYC. Compared with a medicine EPZ6438 which is sold on the market, the squimocin has higher capability of inhibiting the growth of HNSCC, GC and CRC (Cyclic Redundancy Chromatography). In mechanism, the squamocin enhances ubiquitination degradation related to endoplasmic reticulum stress, ubiquitin is triggered through E1 activating enzyme UBA6, ubiquitin is promoted to be transferred to E2 binding enzyme UBE2Z, and then degradation of EZH2 and MYC by E3 ligase FBXW7 is enhanced. The invention provides a novel application of the squamocin in clinical treatment of neck squamous cell carcinoma / gastric cancer / colorectum.

The present invention discloses that GSK126 enhances the response of liver cancer cells to all-trans retinoic acid by increasing the gene expression of retinoic acid receptor γ. The present invention finds that RARγ is the main receptor that mediates the anti-cancer effect of ATRA, and that the EZH2 inhibitor can promote the expression of RARγ by reducing the modification of H3K27me3, further develops the use strategy of EZH2 inhibitor combined with ATRA, and finds that the EZH2 inhibitor combined with ATRA has the effect of synergistically inhibiting tumor proliferation, improves the sensitivity of tumors to ATRA, can promote tumor cell apoptosis and block cells in the G1 phase, and can inhibit tumor cell migration, providing an experimental basis and theoretical basis for the synergistic anti-tumor effect of the two drugs, which is of great significance to the field of tumor treatment.

In some embodiments, therapeutic treatments for a disease such as a cancer are disclosed, including pharmaceutical compositions and methods of using pharmaceutical compositions for treating the cancer wherein the cancer cells overexpress arginine methyltransferase CARM1. In some embodiments, the therapeutic treatments disclosed include methods comprising the step of administering a therapeutically effective dose of an enhancer of zeste homolog 2 (EZH2) inhibitor to a subject, including a human subject, wherein the cancer cells of the subject overexpress arginine methyltransferase CARM1. In some embodiments, the EZH2 inhibitors are administered in conjunction with platinum-based antineoplastic drugs.

The purpose of the present invention is to provide human immortalized myeloid cells (for example, human immortalized monocytes) that can be used in a method for quickly testing a pyrogen remaining in pharmaceutical products, vaccines, medical devices, etc. and has a cytokine (for example, TNF-α)-producing ability without the need for pretreatment. The problem is solved by providing a method for producing human immortalized myeloid cells, the method comprising: (A) a step for forcibly expressing (i) a cMYC gene and (ii) at least one gene selected from the group consisting of a BMI1 gene, an EZH2 gene, an MDM2 gene, an MDM4 gene, and an HIF1A gene in human myeloid blood cells; and (B) a step for freezing, in the presence of a magnetic field, the human immortalized myeloid cells obtained in the step (A).

The invention discloses an in-situ detection system for detecting EZH2 mRNA as well as a preparation method and application of the in-situ detection system. The in-situ detection system comprises a molecular probe compound and a signal amplification compound; the molecular probe compound is constructed from a dCas9-mSA fusion protein and sgRNA of a specific target EZH2 mRNA (messenger Ribonucleic Acid). The signal amplification compound is a metal organic framework nano material encapsulated with fluorescent molecules, and biotin is modified on the metal organic framework nano material; according to the molecular probe compound, Avidin in a dCas9-mSA fusion protein is specifically combined with biotin on the signal amplification compound, so that in-situ labeling and signal amplification of EZH2 mRNA (messenger Ribonucleic Acid) are realized. The in-situ detection system for detecting EZH2 mRNA provided by the invention solves the contradiction that the specificity and the sensitivity are difficult to obtain at the same time in the traditional technology, has the advantages of high sensitivity, strong specificity, good fluorescence quenching resistance, mild operation conditions and the like, can realize in-situ visual detection of tissue slice level EZH2 mRNA, and has a wide application prospect. The kit is especially suitable for auxiliary diagnosis and prognosis evaluation of retinoblastoma.

The invention belongs to the technical field of biology, and relates to a nucleic acid composition for detecting EZH2 gene mutation, a kit and a detection method.The nucleic acid composition comprises a forward primer, a reverse primer, a probe and a closing primer, the binding position of the probe and an EZH2 gene covers the target mutation site of the EZH2 gene, and the closing primer is used for closing the target mutation site of the EZH2 gene. The 5'end of the closed primer and the 3 'end of the forward primer have an overlapped part. The nucleic acid composition disclosed by the invention is used for detecting hot spot mutation of the EZH2 gene, including seven mutation sites of Y646N, Y646F, Y646C, Y646S, Y646H, A682G and A692V, the mutation sites can be subjected to typing, the mutation information of each site can be accurately analyzed only through two-tube reaction, and the sensitivity can reach 0.5%. The detection requirements of a part of more complex clinical samples can be met.