84 results about "Transferase inhibitor" patented technology

The application discloses a specific palmitoyl transferase inhibitor and application thereof, and an active ingredient of the palmitoyl transferase inhibitor is 4-(3-(2-(trifluoromethyl)-9H-thioxanthene-9-ylidene)propyl)-1-piperazine ethanol or a salt thereof. Current palmitoylation inhibitors, 2-bromohexadecanoic acid (2-BP), cerulenin and tunicamycin can all inhibit protein palmitoylation in cells, but all are not selective. And the existing palmitoylation inhibitors are similar to endogenous fatty acids, and inevitably affect lipid metabolism in the body, which limits the clinical application. The application discloses, for the first time, the application of 4-(3-(2-(trifluoromethyl)-9H-thioxanthene-9-ylidene)propyl)-1-piperazine ethanol as a specific palmitoyl transferase inhibitor, and the palmitoyl transferase inhibitor is better in specificity and reversible in inhibition.

The invention relates to the technical field of cancer treatment, and provides application of a lactyltransferase inhibitor in pancreatic cancer and immunotherapy thereof. According to the present invention, the histone lactosyltransferase inhibitor and the anti-programmed death receptor-1 antibody are combined to form the composition for pancreatic cancer and immunotherapy thereof, such that the recognition and the removal of the immune system on the cancer cells can be enhanced, the growth of the pancreatic cancer tumor can be effectively inhibited, and the survival time of the pancreatic cancer patient can be prolonged. The histone lactosyltransferase inhibitor reduces the infiltration level of tumor-associated neutrophil, increases the infiltration level of CD8 positive T cells, reverses the composition of a pancreatic cancer inhibitory immune microenvironment, and generates a synergistic anti-tumor effect with an anti-programmed death receptor-1 antibody. The traditional Chinese medicine composition is suitable for early-stage, middle-stage and late-stage treatment of pancreatic cancer, improves the survival rate and the treatment effect of pancreatic cancer patients, remarkably reduces the side effects of treatment and improves the living quality of the pancreatic cancer patients.

The invention relates to the technical field of medicine analysis, in particular to a method for analyzing mutagenic impurities in a small molecule fungal inositol acyltransferase 1 inhibitor raw material medicine, the analysis method can be used for trace detection of potential mutagenic impurities I and II in the raw material medicine, the limit of quantitation concentration of the impurity I is not higher than 0.53 ng / ml, and the limit of quantitation concentration of the impurity II is not higher than 0.53 ng / ml. The detection limit concentration of the impurity I is not higher than 0.27 ng / ml; the quantitation limit concentration of the impurity II is not higher than 0.52 ng / ml, and the detection limit concentration of the impurity II is not higher than 0.26 ng / ml. The analysis method suitable for the mutagenic impurities in the small-molecule fungal inositol acyltransferase 1 inhibitor bulk drug is high in sensitivity and high in specificity, and the blank solvent does not interfere with detection of the impurities.

A pharmaceutical composition comprising a protein arginine methyltransferase 5 (PRMT5) inhibitor and a methionine adenosyltransferase IIα (MAT2A) inhibitor. The pharmaceutical composition can be used for treating various cancers, comprising solid tumors. The combined product can be used for treating any number of diseases associated with PRMT5 and / or MAT2A.

The invention discloses an (E)-6-(4-carbonyl phenyl) hex-2-ene-1-ketone compound as well as a preparation method and application thereof, the compound can be used as a palmitoyl transferase inhibitor, and the palmitoylation process of substrate protein is further inhibited by inhibiting DHHC protein, so that the inhibition effect on tumor cells is achieved. Embodiments show that the compounds have different degrees of anti-proliferative activity to different cancer cells and different degrees of enzyme inhibitory activity to DHHC proteins, and part of the compounds have better inhibitory activity to cancer cells and DHHC proteins than positive control drugs, and can be further developed into a new generation of antitumor drugs.

Disclosed herein are compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein A and A′ are each independently selected from the group consisting of: (a1), (a2), (a3), (4) and (a5) and B, B′, X and Y have the meanings provided herein, that are methionine adenosyltransferase 2A (MAT2A) inhibitors. Also disclosed are pharmaceutical compositions comprising such compounds and methods of treating diseases treatable by inhibition of MAT2A such as cancer.

The present invention relates to the use of carnitine palmitoyltransferase 1 inhibitors in the treatment of heart failure with preserved ejection fraction. The use in particular is the use of the carnitine palmitoyltransferase (CPT1) inhibitor Etomoxir for the prevention and / or treatment of heart failure with preserved ejection fraction by oral administration.

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.

The invention relates to application of a lysine methyltransferase DOT1L inhibitor in preparation of a medicine for treating hepatic ischemia reperfusion injury, and belongs to the technical field of biological medicine. The lysine methyltransferase DOT1L inhibitor is SGC0946, and the lysine methyltransferase DOT1L inhibitor is The invention discloses a lysine methyltransferase DOT1L inhibitor for the first time, and particularly discloses new application of SGC0946 in preparation of a medicine for treating liver ischemia reperfusion injury. The invention proves that the expression level of the DOT1L in a mouse suffering from the hepatic ischemia reperfusion injury is obviously improved, so that the methylation level of H3K79 is obviously increased, the levels of glutamic-pyruvic transaminase and glutamic oxalacetic transaminase are obviously increased, and ferroptosis marker genes Ptgs2 and Cac1 are obviously increased, which indicates that the DOT1L can be used as a target spot for treating the hepatic ischemia reperfusion injury and can be used for treating the hepatic ischemia reperfusion injury. The lysine methyltransferase DOT1L inhibitor can be used for preparing the medicine for treating the hepatic ischemia reperfusion injury.

The present invention relates to the use of a lysine methyltransferase DOT1L inhibitor in the preparation of a medicament for treating liver ischemia-reperfusion injury, belonging to the technical field of biomedicine. The lysine methyltransferase DOT1L inhibitor is SGC0946. The present invention discloses for the first time the new use of a lysine methyltransferase DOT1L inhibitor, especially SGC0946, in the preparation of a medicament for treating liver ischemia-reperfusion injury. The present invention confirms that the expression level of DOT1L in mice with liver ischemia-reperfusion injury is significantly increased, which in turn leads to a significant up-regulation of the H3K79 methylation level, a significant increase in the levels of alanine aminotransferase and aspartate aminotransferase, and the ferroptosis marker genes Ptgs2 and Chac1 are significantly up-regulated, indicating that DOT1L can be used as a target for treating liver ischemia-reperfusion injury, and a lysine methyltransferase DOT1L inhibitor can be used to prepare a medicament for treating liver ischemia-reperfusion injury.

The invention relates to a class of compounds useful as Hedgehog Acyltransferase inhibitors, as well as the treatment or prevention of diseases associated with the Hedgehog signalling pathway using the compounds of the present invention. In one aspect, the present invention provides a compound of formula (I) below.

The invention relates to the technical field of oral medicine, in particular to a DNMTi and ZIF-8 nano-complex and application thereof.The DNMTi and ZIF-8 nano-complex is technically characterized in that in-situ synthesized zeolite imidaze-8 (ZIF-8) is adopted for delivering a DNA methyltransferase inhibitor (DNMTi), dental pulp stem cell (DPSC) cell spheres are combined, the DNMTi and ZIF-8 nano-complex can be used for bionic therapy, the activity of medicine is prolonged, and the effect of treating dental pulp stem cells is achieved. And zinc ions are continuously released to activate a PI3K-AKT signal channel, so that the dentin differentiation of stem cells and the generation of blood vessels are promoted. Through accurate simulation of a tooth development microenvironment, the biomimetic therapy can realize regeneration of a dental pulp-dentin complex. The therapy for simulating the tooth development process not only solves the key problems in the dental tissue engineering, but also opens up a new direction for treating the dental pulp and periapical diseases, and highlights the wide application prospect in regenerative medicine.

This invention discloses a high-throughput screening method for monkeypox virus (MPXV) N7-methyltransferase (N7-MTase) inhibitors based on fluorescence polarization technology and its application. This method uses MPXV E1... CTD Using the / E12 protein complex as a target, and leveraging the specific binding characteristic of the fluorescent probe FL-NAH to the target catalytic center, small molecule inhibitors that competitively bind to the SAM binding site are screened by monitoring changes in fluorescence polarization signals. This invention yielded a series of candidate compounds with significant inhibitory activity. Experiments demonstrated that these inhibitors exhibit strong inhibitory effects on MPXV N7-MTase, with a biochemical IC50 level of [missing information]. 50 Preferably, the concentration can reach 4.65 μM; at the cellular level, the compound exhibits a clear attenuation effect against poxviruses, with an EC50 value of [missing value]. 50 The range is up to 46.75 μM, and it has low cytotoxicity (CC). 50 >200 μM).

Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

The present invention relates to the technical field of cancer treatment, and provides the use of lactyltransferase inhibitors in pancreatic cancer and its immunotherapy. The present invention uses a histone lactyltransferase inhibitor in combination with an anti-programmed death receptor-1 antibody as a composition for pancreatic cancer and its immunotherapy, which can enhance the immune system's recognition and clearance of cancer cells, effectively inhibit the growth of pancreatic cancer tumors, and prolong the survival time of pancreatic cancer patients. Histone lactyltransferase inhibitors reduce the infiltration level of tumor-associated neutrophils, increase the infiltration level of CD8-positive T cells, reverse the composition of the inhibitory immune microenvironment of pancreatic cancer, and produce a synergistic anti-tumor effect with anti-programmed death receptor-1 antibodies. It is suitable for the early, middle and late treatment of pancreatic cancer, improves the survival rate and treatment effect of pancreatic cancer patients, and significantly reduces the side effects of treatment, thereby improving the quality of life of pancreatic cancer patients.

This invention relates to the application of methyltransferase inhibitors as adjuvants for respiratory syncytial virus (RSV) vaccines and allergy vaccines. Methyltransferase inhibitors, as adjuvants for RSV vaccines or allergy vaccines, can target and regulate the antigen presentation function of vaccine-induced memory dendritic cells (DCs), thereby regulating the balance of T cell responses and balancing the dominant Th2 and / or Th17 cellular immune responses induced by RSV vaccines or allergy vaccines. This allows the vaccine recipient to develop a balanced immune memory, providing protection while preventing the occurrence of vaccine-enhanced inflammatory diseases when RSV infection or allergen stimulation occurs, thus being both safe and effective.

Methods and compositions for treating cancer e.g., liver cancer in a subject in need thereof are provided. Compositions including an effective amount of an 1-Acylglycerol-3-Phosphate O-Acyltransferase 4 (AGPAT4) inhibitor alone, or in combination with a kinase inhibitor and methods of use thereof for treating cancer are disclosed. The composition includes one or more small molecule inhibitors, inhibitory nucleic acids, or inhibitor proteins in a pharmaceutically acceptable carrier. Administration of the AGPAT4 inhibitor, alone or in combination with a kinase inhibitor is effective to reduce cancer cell proliferation or viability in a subject with cancer. Methods of selecting and treating subjects with cancers, particularly liver cancer are also provided.

The present invention relates to series of peptidomimetic compounds as an inhibitor targeting protein N-terminal methyltransferase pharmacological pathway. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases caused by abnormal protein methyltransferase pathway, including cancer, inflammation, neurodegenerative and cardiovascular diseases, are within the scope of this disclosure.

Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors nicotinamide N-methyltransferase (NNIMT). Also disclosed are pharmaceutical compositions comprising a compound disclosed herein. Related methods of treating cancer in a subject and methods of inhibiting tumor growth in subject are also disclosed.

Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors nicotinamide N-methyltransferase (NNMT). Also disclosed are pharmaceutical compositions comprising a compound disclosed herein. Related methods of treating cancer in a subject and methods of inhibiting tumor growth in subject are also disclosed.

To provide a new antitumor agent.SOLUTION: The present invention provides an antitumor agent containing a glutathione concentration lowering agent or a glutathione S-transferase inhibitor as an active ingredient to be administered simultaneously with an aldehyde dehydrogenase inhibitor, or an antitumor agent containing an aldehyde dehydrogenase inhibitor as an active ingredient to be administered simultaneously with an effective amount of a glutathione concentration lowering agent or a glutathione S-transferase inhibitor, or a combination drug containing an aldehyde dehydrogenase inhibitor and a glutathione concentration lowering agent or a glutathione S-transferase inhibitor as active ingredients. The aldehyde dehydrogenase inhibitor is a compound represented by the following formula (I) or a pharmacologically acceptable salt thereof.SELECTED DRAWING: None

Disclosed herein are serine palmitoyltransferase inhibitors of formula (I); or a pharmaceutically acceptable salt form thereof. The variables in formula (I) are described herein. Also disclosed is a method of treating a subject with a disease characterized by elevated ceramide levels or a disease or condition that is mediated by serine palmitoyltransferase, comprising administering an effective amount of the disclosed serine palmitoyltransferase inhibitors disclosed herein.

Disclosed is a methionine adenosyltransferase 2A heterocyclic inhibitor. The structure of the methionine adenosyltransferase 2A inhibitor is represented by general formula I, wherein at most two of W, X, Y and Z are simultaneously N, and R1 and R2 are each independently selected from a 6- to 10-membered aryl or a 9- to 18-membered benzoheterocyclyl. Also disclosed is a preparation method therefor. The compound of general formula I has significant inhibitory activity of methionine adenosyltransferase 2A and can be used for treating methionine adenosyltransferase 2A-mediated diseases.

The present invention relates to series of peptidomimetic compounds as an inhibitor targeting protein N-terminal methyltransferase pharmacological pathway. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases caused by abnormal protein methyltransferase pathway, including cancer, inflammation, neurodegenerative and cardiovascular diseases, are within the scope of this disclosure.

The present invention relates to a compound, the compound is a compound represented by a formula (I), or an isomer, an isotope derivative, a polymorphic substance, a prodrug, a pharmaceutically acceptable salt or a solvate (I) thereof, and the definitions of A, B and C are the same as the definitions in the specification. Also provided are pharmaceutical compositions and compounds of formula (I) for use in methods of treating related diseases by inhibition of MAT2A, including some cancers in which a gene encoding a methylthioadenosine phosphorylase (MTAP) is deleted and / or not fully functioning.

The invention belongs to the field of biological medicines, and particularly discloses a novel application of a histone methyltransferase G9a inhibitor in preparation of a medicine for treating xerophthalmia. The invention discovers that the histone methyltransferase G9a inhibitor has an autophagy regulation effect for the first time, and by using the G9a inhibitor UNC0642, the rising inflammatory factors, active oxygen levels and apoptosis rate in the xerophthalmia can be reduced, and the symptoms of the xerophthalmia can be relieved in an animal model. The invention provides a potential molecular therapeutic target for effectively treating xerophthalmia, and has good practical application value.

The present invention relates to series of peptidomimetic compounds as an inhibitor targeting protein N-terminal methyltransferase pharmacological pathway. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases caused by abnormal protein methyltransferase pathway, including cancer, inflammation, neurodegenerative and cardiovascular diseases, are within the scope of this disclosure.

To provide a novel inflammasome inhibitor.SOLUTION: An inflammasome inhibitor comprising, as an active ingredient, an inhibitor of 3-mercaptopyruvate sulfurtransferase.SELECTED DRAWING: Figure 2

The present invention relates to the technical field of pharmaceutical analysis, and in particular to an analytical method for mutagenic impurities in the raw material drug of a small molecule fungal inositol acyltransferase 1 inhibitor. This analytical method can be used for trace detection of potential mutagenic impurity I and impurity II in the raw material drug. The limit of quantitation concentration of impurity I is not higher than 0.53 ng / ml, and the limit of detection concentration of impurity I is not higher than 0.27 ng / ml; the limit of quantitation concentration of impurity II is not higher than 0.52 ng / ml, and the limit of detection concentration of impurity II is not higher than 0.26 ng / ml. The analytical method provided by the present invention for mutagenic impurities in the raw material drug of a small molecule fungal inositol acyltransferase 1 inhibitor has high sensitivity and strong specificity, and the blank solvent does not interfere with the detection of each impurity.

The invention provides a method for regulating and controlling the transcriptional activity of a PAFAH1B1 gene and application of the method, and belongs to the technical field of gene expression regulation and control. The method comprises the step of influencing the methylation level of a PAFAH1B1 gene promoter region by using a gRNA fragment, a DNA methyltransferase inhibitor or an RNA interference fragment of DNA methyltransferase. The method is applied to the ovarian granulosa cells, and under different treatments, the mRNA level and the protein expression level of PAFAH1B1 in the ovarian granulosa cells can be remarkably promoted or inhibited. According to the application, the obvious influence of DNA methylation on the transcriptional activity of the PAFAH1B1 gene in the ovarian granular cells is determined for the first time, the position of the DNA methylation applied to the promoter region of the PAFAH1B1 gene is determined for the first time, and the mechanism that the DNA methylation affects the expression of the PAFAH1B1 gene by changing the chromatin structure of the promoter region of the PAFAH1B1 gene is disclosed, so that the expression of the PAFAH1B1 gene in the ovarian granular cells is improved. The invention provides a simpler and more effective new way for regulating and controlling granular cell functions and ovarian development, and has important application value for subsequent research on mammal ovarian granular cell functions, follicular development and initial estrus initiation.