71 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.

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 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.

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 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 present invention belongs to the technical field of cellular anti-aging, and specifically relates to a small-molecule compound composition capable of reversing the senescence of an adult stem cell and restoring the regeneration activity thereof, and a method for reversing cellular senescence by means of using a chemical small-molecule composition and the use thereof. The composition capable of reversing cellular senescence comprises a WNT / β-catenin agonist, a TGF-β receptor inhibitor, an RAR agonist, a Smoothened receptor agonist, a multi-target inhibitor of the VEGFR and PDGFR families, a histone methyltransferase inhibitor, and a JAK1 / 2 inhibitor. The composition effectively solves the problem of the weak proliferation and regeneration potential of senescent adult stem cells, effectively reverses the senescence of the adult stem cells and maintains the intrinsic biological characteristics of the cells, and can thus improve and enhance the efficacy of clinical autologous cell transplantation therapy and cell derivative therapy.

The present invention relates to a biaryl derivative compound, which exhibits the activity of a diacylglycerol acyltransferase 2 (DGAT2) inhibitor and is represented by chemical formula (1), a pharmaceutical composition comprising same as an active ingredient, and a use thereof.

The present disclosure refers to therapeutic combinations and pharmaceutical compositions comprising glycolysis inhibitors / modulators and prenyltransferase inhibitors for treating brain tumors. In particular, the disclosure describes therapeutic combinations and pharmaceutical compositions of dichloroacetate (DCA) and perillyl alcohol (POH) useful for treating brain cancers such as glioblastoma multiforme (GBM). Additionally, the disclosure provides methods for treating GBM and other forms of brain cancer using the same.

Described herein are crystalline forms of small molecule methionine adenylyltransferase 2a (MAT2A) inhibitors and pharmaceutical compositions thereof, and methods of use thereof in the treatment of diseases or conditions that benefit from treatment with methionine adenylyltransferase 2a (MAT2A) inhibitors.

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 inhibitory 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 an amide derivative compound, which exhibits the activity of a diacylglycerol acyltransferase (DGAT) 2 inhibitor and is represented by chemical formula (1), a pharmaceutical composition comprising same as an active ingredient, and a use thereof.