37 results about "EZH2" patented technology

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.

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.

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 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.

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.

For example, to provide a method for identifying or selecting patients who are most likely to benefit from treatment with telomerase inhibitors such as imetelstat. [Solution] This disclosure provides a method for identifying or selecting patients who are most likely to benefit from treatment with telomerase inhibitors, such as imetelstat, by testing for high molecular weight risk (HMR) based on the absence of mutations in each of JAK2, CALR, and MPL, and / or the presence of a mutation in at least one of the following genes: ASXL1, EZH2, SRSF2, and IDH1 / 2. These patients may have myelofibrosis. This disclosure also provides a method for treating myelofibrosis, the method of which includes identifying such patients.

Provided herein are methods of treating cancer using a combination of a compound provided herein (e.g., Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, or Compound 7, or a stereoisomer or mixture of stereoisomers, a pharmaceutically acceptable salt, a tautomer, a prodrug, a solvate, a hydrate, a co-crystal, a clathrate, or a polymorph thereof) and a second active agent. The second active agent is one or more of a PLK1 inhibitor, a BRD4 inhibitor, a BET inhibitor, a NEK2 inhibitor, a AURKB inhibitor, a MEK inhibitor, a PHF19 inhibitor, a BTK inhibitor, a mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BIRC5 inhibitor, or a DNA methyltransferase inhibitor.

The present invention relates to a method for producing a modified mRNA construct in which a nucleotide derivative is coupled to the 3' terminus of mRNA by non-enzymatic extension using a nucleotide activated with imidazole or 2-aminoimidazole or a derivative thereof, and to enhancement of antigen protein translation efficiency resulting therefrom. When the modified mRNA construct of the present invention is applied to expression of an anticancer gene, an apoptosis-inducing effect in cancer cells can increase, and an anticancer effect in which EZH2 expression is reduced can be exhibited.

The present invention provides SETD2 protein inhibitors, and methods of using SETD2 protein inhibitors and optionally a second therapeutic agent in the treatment of a disease, disorder, or condition in a subject, wherein the second therapeutic agent comprises one or more glucocorticoid receptor agonists, one or more immunomodulatory drugs, one or more proteasome inhibitors, one or more Bcl-2 inhibitors, one or more pleiotropic pathway modulators, one or more XPOl inhibitors, one or more histone deacetylase inhibitors, or one or more EZH2 inhibitors, or combinations thereof.

The present invention relates to a pharmaceutical composition for the prevention or treatment of cancer comprising an EZH2 inhibitor and a BTK inhibitor, and it has been confirmed that the therapeutic effect is significantly superior not only in Ebstein-Barr virus (EBV)-associated lymphoma, which has had low therapeutic efficacy until now, but also in other types of cancer.

Provided herein are methods of treating cancers having at least one ARID 1 A mutation with (R)-7-chloro-2-((1r,4R)-4-(3-methoxyazetidin-1-yl)cyclohexyl)-2,4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihy-dropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

This invention discloses a polypeptide combination for inhibiting tumor invasion and metastasis, belonging to the field of therapeutic technology for metastatic breast cancer. The polypeptide combination comprises two polypeptides, each containing a targeting peptide P1 and a targeting peptide P2, respectively. A membrane-penetrating peptide is attached to the N-terminus of both targeting peptides P1 and P2. Histone-lysine N-methyltransferase EZH2 preferentially methylates the aforementioned polypeptide combination, thereby reducing the methylation of lysine residues at positions 53 and 333 of the SMAD3 protein, thus inhibiting tumor cell invasion and metastasis.

The invention discloses application of curculigoside in preparation of a medicine for preventing or treating renal fibrosis, and belongs to the technical field of biological medicine. In an in-vivo experiment, expression levels of Vimentin and alpha-SMA in kidney tissues of UUO model mice can be reduced through intraperitoneal injection of curculigoside, so that cell phenotypic transformation induced by TGF-beta1 is reduced, the collagenous fiber deposition area in Masson dyeing is reduced, the expression level of Collagen I protein in the kidney tissues of the UUO model mice is reduced, and the fibrosis process of the kidney tissues is reduced. Proved by signal generation analysis and cell thermal migration experiments, curculigoside can be combined with EZH2, which prompts that curculigoside can inhibit the fibrosis process through a targeted EZH2 pathway. It is proved for the first time that curculigoside has the effect of relieving renal fibrosis, and a new thought is provided for medicine development of curculigoside in the kidney disease direction.

The application discloses application of YG1702 in preparation of a drug for resisting Ewing's sarcoma, and YG1702 can effectively inhibit Ewing's sarcoma proliferation, self-renewal and in-vivo tumorigenicity by inhibiting expression of an Ewing's sarcoma ALDH18A1 gene, and can inhibit expression of an EWS-FLI1 fusion gene of the Ewing's sarcoma and downstream target genes EZH2, ID2, PTPL1, CCND1 and VEGFA, and can become a potential target therapy candidate small molecule, and the application has potential clinical value for finding a new Ewing's sarcoma treatment target and improving a combined treatment effect of Ewing's sarcoma patients.

Provided are amide compounds, a preparation method therefor, and use thereof in the medical field. Specifically, provided are small molecule amide compounds. Such compounds are inhibitors of enhancer of Zeste homolog 2 (EZH2), and can be used for preventing and / or treating related diseases mediated by EZH2, including tumors, myeloproliferative diseases or autoimmune diseases.

The application provides an application of vascular endothelial cell histone methyltransferase Ezh2 in preparation of a medicine for preventing and treating sepsis-associated encephalopathy and model construction, relates to the field of biomedical technology, and has the primary purpose of providing a drug target for preventing and treating SAE, namely, EZH2 in vascular endothelial cells. The application also provides an endothelial cell specific Ezh2 gene conditional knockout mouse model, the model has a high sensitivity and a high stability of BBB damage phenotype, and can be used for SAE pathogenesis research and drug screening. The application further has the purpose of providing SAE treatment drugs, diagnostic markers and screening methods based on the new target and the new model. In the application, a mouse Ezh2 gene conditional knockout and an induced conditional knockout-CLP high-sensitivity SAE model are successfully constructed. The model not only overcomes the problem of systemic knockout lethality, but also has a BBB damage and neuroinflammation phenotype which is much more serious and stable than that of a traditional CLP model, thereby providing an irreplaceable tool for drug research and development.

The invention provides a compound with EZH2 specific inhibitor activity and application of the compound. The compound provided by the invention has extremely strong inhibitory activity and good drug properties, and can be used for treating diseases and / or symptoms of the diseases mediated by EZH1, EZH2 and / or PRC2.