54 results about "Inhibition enzyme" patented technology

Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and / or conditions associated with inflammation.

This disclosure relates to antibodies that bind an epitope present on CD73 expressed at the surface of cells, including tumor cells, and that inhibit the enzymatic (ecto-5′ nucleotidase) activity of the CD73 enzyme. Such agents can be used for the treatment of diseases such as cancers.

The present invention is directed to a compound of formula I:or any stereoisomeric form of the compound of the formula I or a mixture of these forms in any ratio or a physiologically acceptable salt of the compound of the formula I which inhibit the enzyme TAFIa (activated thrombin-activatable fibrinolysis inhibitor), and to a process for their preparation and to their use to treat described diseases where the substituents are as described in the specification.

Compounds of Formulas I-XLIII are identified as direct inhibitors of p97 ATPase or of the degradation of a p97-dependent ubiquitin-proteasome system (UPS) substrate. Methods and compositions are disclosed for inhibiting p97 ATPase and the degradation of a p97-dependent UPS substrate, and for identifying inhibitors thereof.

The invention discloses a thiacloprid and acetamiprid monoclonal antibody hybridoma cell strain GW and application thereof, and belongs to the field of food security immunodetection. Thiacloprid and acetamiprid complete antigen of the strain is uniformly mixed with an equal amount of QuickAntibody-Mouse 5W adjuvant, and is injected to BALB / c mice through leg muscle. The dosage is 100mu g / mouse for the first time of immunization, the dosage is 50[mu]g / mouse for multiple times of intensified immunization, the immunization is implemented at an interval of 21 days, and thiacloprid and acetamiprid complete antigen (25[mu]g / mouse, without adjuvant) is adopted for immunization impact for the last time. Splenocyte of high-potency low IC50 mice is taken and fused with mouse myeloma cells by using a PEG method, indirect competitive inhibition enzyme-linked immunosorbent assay is adopted for screening, and three times of subcloning is implemented, so as to obtain the hybridoma cell strain. A monoclonal antibody secreted from the cell strain has relatively good specificity and detection sensitivity (the IC50 values are 0.1ng / mL and 0.4ng / mL respectively) for thiacloprid and acetamiprid, detection on the residual amounts of thiacloprid and acetamiprid in water, fruits and vegetables and cereals can be achieved, conditions are provided for immunodetection on thiacloprid and acetamiprid residues in food can be provided, and practical use values can be made.

Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian protein farnesyltransferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One protein farnesyltransferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. Also disclosed are methods and compositions for the preparation of farnesyltransferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme. The most potent inhibitors are ones in which phenylalanine occurs at the third position of a tetrapeptide whose amino terminus is cysteine.

The invention relates to a competitive inhibition enzyme-linked immunoassay (ELISA) method of grass carp interleukin 10 (IL-10). The method comprises the following steps of: immunizing a New Zealand white rabbit by utilizing grass carp interleukin 10 proteins which is expressed in a recombined way as an immunogen to obtain a polyclonal antibody; marking the antibody by utilizing horseradish peroxidase; and finally, establishing the competitive inhibition ELISA method by taking the recombined grass carp interleukin IL-10 protein as a covered antigen, wherein the competitive inhibition ELISA method can be used for the protection detection of the grass carp interleukin 10. The detection range of the ELISA method is 0.1-100 ng / mL. By utilizing the polyclonal antibody and the competitive inhibition ELISA method, the cost is low, and the stability and the repeatability are good. The conventional method is that the competitive inhibition ELISA method is firstly established to detect protection expression of the grass carp interleukin 10.

The invention discloses application of a compound which is shown in a formula I and has a mother nucleus structure in preparing an MMP-9 enzymatic activity inhibitor. The invention also discloses a method for screening substances having the function of inhibiting the MMP-9 enzymatic activity.

The present invention encompasses assays to identify compounds that inhibit the enzymatic activity of MIF which catalyzes the tautomerization of MIF-substrates, such as D-dopachrome to DHICA. In general, the assay is conducted in vitro by adding, mixing or combining MIF and a suitable substrate in the presence or absence of a test compound, and measuring the tautomerization of the substrate. The test compounds that inhibit tautomerization in the assay are identified as MIF inhibitors.

The invention relates to a competitive inhibition enzyme-linked immunosorbent assay (ELISA) method for grass carp tumor necrosis factors alpha. The method comprises the following steps of: 1, determining the concentration of coating antigens and the optimal dilution ratio of polyclonal antibodies; 2, establishing the competitive inhibition ELISA method, and coating an ELISA plate of grass carp tumor necrosis factor alpha protein to obtain antigens immobilized on the ELISA plate; mixing enzyme-labeled antibodies and an antigen mixed solution, and performing competitive binding on the solution and the antigens immobilized on the ELISA plate; washing the ELISA plate and developing the color of the substrate; and reading holes of the ELISA plate to obtain the light absorption value of each hole, calculating the inhibition rates of a standard antigen and a sample to be detected according to the read light absorption values respectively, and calculating the concentration of the sample to be detected according to the inhibition rates. The method has the advantages that a quick and efficient detection means is provided for detecting the protein expression level of the grass carp tumor necrosis factors alpha; and the method is stable, reliable and low in cost.

The invention provides a pyridine compound WXSA-051B which is designed and synthesized for aiming at an enzyme active site to inhibit RBP2 enzyme activity, and also provides a preparation method of the pyridine compound. Tests prove that the compound can obviously increase the level of H3K4me3 protein in a human gastric cancer cell BGC-823, has an obvious effect of inhibiting RBP2 enzyme activity,and can reduce the migration ability of the human gastric cancer cell BGC-823. The compound provided by the invention can be used as a gastric cancer inhibitor for preparing an anti-gastric cancer drug. The structure of the compound is as shown in the description.

The invention relates to the related fields of immunology, pharmacy and medicine, discloses a method for preparing a hybridoma cell line and a monoclonal antibody based on B cell epitopes of dipeptidyl peptidase 4 (DPP-4) and an application thereof, and especially, relates to small molecular antigen peptides prepared by coupling the B epitopes of DPP-4 with intramolecular carrier peptides and quickly obtained by a synthetic method; the small molecular antigen peptides immunize mice to produce strong immune response, and can be used for preparing immune spleen lymphocytes and preparing hybrid tumor cells, antibodies and the like. The monoclonal antibody is secreted by the hybridoma cell line (having the preservation number of CCTCC No:C2017227), is a Th2 antibody, is IgG1 in the mice, inhibits the enzyme activity of DPP-4, is specifically combined with DPP-4, can develop a DPP-4 detection reagent and a DPP-4 inhibitor, can significantly reduce blood sugar, uric acid and four indexes ofcreatinine blood lipid, increases GLP-1, regulates oxidative stress and immune balance from Th1 trending to Th2, and reduces pancreatic inflammation; prepared drugs are used for preventing and treating diabetes and complications thereof, hyperuricemia, gout, kidney and liver diseases, hyperlipidemia, AS, cardiovascular diseases and Th1-related diseases.

The invention provides honokiol and application of magnolol in preparation of an MCR-1 enzyme inhibitor, provides honokiol and novel medical application of magnolol in preparation of an MCR-1 enzyme inhibitor and discloses honokiol and magnolo which can inhibit the activity of an MCR-1 enzyme and restore the sterilization activity of polymyxin to MCR-1 enteric bacilli. In an in-vivo experiment, the honokiol and magnolol are combined and applied to bacterial infection of the polymyxin for MCR-1 expression, particularly have a good treatment effect on infection caused by MCR-1 positive enteric bacilli and have a wide medical application range.

The subject invention concerns peptide molecules that specifically inhibit the enzymatic function of tyrosine kinases, including the JAK and EGF receptor (EGFR) family of kinases, to autophosphorylate, i.e., to transfer a phosphate group from ATP to an amino acid in the kinase. Phosphorylation of proteins is the most fundamental method for signal transduction among proteins in a cell. Inhibition of tyrosine kinase autophosphorylation activities inhibits the enzyme's signaling and shuts down the functioning pathways originating from the enzyme. The JAK2 and EGFR tyrosine kinases are involved in both inflammatory disorders and cancer. In these disorders, the tyrosine kinases can often be activated in an uncontrolled fashion. The subject application also concerns antibodies that bind to a tyrosine kinase autophosphorylation site. The subject invention also concerns pharmaceutically acceptable formulations of the subject peptides and antibodies, and methods for treating inflammatory and oncological disorders by inhibiting tyrosine kinase signaling in these situations by administering a peptide or antibody of the present invention.

This disclosure relates to antibodies that bind an epitope present on CD73 expressed at the surface of cells, including tumor cells, and that inhibit the enzymatic (ecto-5′ nucleotidase) activity of the CD73 enzyme. Such agents can be used for the treatment of diseases such as cancers.

The invention relates to a competitive inhibition enzyme-linked immunosorbent assay (ELISA) method for grass carp tumor necrosis factors alpha. The method comprises the following steps of: 1, determining the concentration of coating antigens and the optimal dilution ratio of polyclonal antibodies; 2, establishing the competitive inhibition ELISA method, and coating an ELISA plate of grass carp tumor necrosis factor alpha protein to obtain antigens immobilized on the ELISA plate; mixing enzyme-labeled antibodies and an antigen mixed solution, and performing competitive binding on the solution and the antigens immobilized on the ELISA plate; washing the ELISA plate and developing the color of the substrate; and reading holes of the ELISA plate to obtain the light absorption value of each hole, calculating the inhibition rates of a standard antigen and a sample to be detected according to the read light absorption values respectively, and calculating the concentration of the sample to be detected according to the inhibition rates. The method has the advantages that a quick and efficient detection means is provided for detecting the protein expression level of the grass carp tumor necrosis factors alpha; and the method is stable, reliable and low in cost.

The invention relates to a schistosoma japonicum thioredoxin glutathione reductase Sj TGR single-domain antibody and a preparation method thereof, and belongs to the technical field of molecular biology, immunology and pharmacy of a pharmaceutical technology. The invention provides a recombinant phage display library for displaying an Sj TGR protein single-domain antibody, the Sj TGR protein resistant single-domain antibody and a preparation method thereof. The Sj TGR resistant single-domain antibody disclosed by the invention can be specifically combined with an Sj TGR protein and / or has Sj TGR inhibition activity and can be used for preparing a new drug for curing schistosomiasis or a targeting vector of the drug for cure. The schistosoma japonicum thioredoxin glutathione reductase Sj TGR single-domain antibody disclosed by the invention lays a good foundation for developing the new drug for curing the schistosomiasis and a new curing method and has important significance on controlling schistosomiasis prevalence.

The invention provides application of oridonin and / or a prodrug thereof in preparation of a medicine for inhibiting SARS-CoV-2. The oridonin can target Mpro protease in the SARS-CoV-2 and significantly inhibit the enzyme activity, effectively inhibits the RNA replication of the SARS-CoV-2 and reduces the activity of the SARS-CoV-2, it is indicated that the small molecule oridonin can be used for treating or preventing the novel coronavirus pneumonia infected by the SARS-CoV-2 and an efficient, safe and novel natural medicine source without toxic and side effects is provided for treatment of novel coronavirus pneumonia.

The invention discloses a urine stabilization protective reagent. The urine stabilization protective reagent comprises NaCI, a fixing agent, a preservative, an antioxidant, kojic acid and / or flavone,EDTA dipotassium salt, sodium citrate and heparin. The urine stabilization protective reagent disclosed by the invention has the advantages that firstly, visible components in urine can be effectivelypreserved and are not easy to gather and crack, the degradation of enzymes is inhibited, and a guarantee is provided for cell or enzyme detection; secondly, the propagation and growth of microorganisms are controlled, premature degradation or oxidation of human metabolites after contact with the external environment is prevented, and conditions are provided for the accuracy of various detections;and thirdly, the protection of the natural acidity of the urine is noticed, and protective blending is carried out for urine acidity measurement. In conclusion, the invention provides a novel reliable method for stable preservation of a urine sample.

A method of treating a patient with multiple drugs using adjusted phenotypes of CYP450 enzymes to assess the risk of adverse drug reactions occurring due to drug-enzyme interactions. CYP450 enzyme genotypes and phenotypes are measured in a patient. The phenotypes are scored numerically. The drugs intended for treatment are scored numerically for their ability to induce or inhibit the CYP450 enzymes. The drug scores are used to adjust the CYP450 phenotype scores relative to inducing or inhibiting the enzymes. An accurate adjusted phenotype score for a given CYP450 enzyme is converted to an accurate adjusted phenotype. Any of the intended drugs for treatment that are substrates for the given CYP450 enzyme can be evaluated for risk of an adverse drug reaction based on the adjusted phenotype. This method of rapid risk assessment provides an accurate basis for decisions regarding changes in dose, eliminating a drug, or replacing a drug.

The present invention is directed to novel compounds. These compounds can be useful in inhibiting the activity of GGTase I. The compounds can also be used as anti-cancer therapeutics including as part of methods for treating cancer, in assays, and in kits.

The invention provides a method for designing a DPP-IV (dipeptidyl peptidase-IV) inhibitory peptide by a computer-aided drug, the DPP-IV inhibitory peptide and application of the DPP-IV inhibitory peptide. The method comprises the steps of establishing a database and dividing the database into an internal training set and an external test set; constructing the structure of the polypeptide in the database; carrying out molecular docking on the polypeptide and DPP-IV to select a conformation with the highest score; carrying out superposition by taking the tripeptide IPI as a template molecule and taking a peptide bond as a public skeleton; manually adjusting the bond angle of each peptide to improve the model fitting degree, wherein the training set is an established target model, and the test set is used for testing the prediction capability of the model; calculating the pIC50 of the peptide in the test set by using the training set, and comparing the calculated pIC50 of the peptide with the pIC50 obtained by the experiment; then exporting an equipotential diagram of the training set to guide the design of the DPP-IV inhibitory peptide; and finally obtaining the novel DPP-IV inhibitory peptide. The novel peptide designed and obtained by the invention has very high activity of inhibiting DPP-IV enzyme.

The present invention encompasses assays to identify compounds that inhibit the enzymatic activity of MIF which catalyzes the tautomerization of MIF-substrates, such as D-dopachrome to DHICA. In general, the assay is conducted in vitro by adding, mixing or combining MIF and a suitable substrate in the presence or absence of a test compound, and measuring the tautomerization of the substrate. The test compounds that inhibit tautomerization in the assay are identified as MIF inhibitors.

The invention relates to a competitive inhibition enzyme-linked immunoassay (ELISA) method of grass carp interleukin 10 (IL-10). The method comprises the following steps of: immunizing a New Zealand white rabbit by utilizing grass carp interleukin 10 proteins which is expressed in a recombined way as an immunogen to obtain a polyclonal antibody; marking the antibody by utilizing horseradish peroxidase; and finally, establishing the competitive inhibition ELISA method by taking the recombined grass carp interleukin IL-10 protein as a covered antigen, wherein the competitive inhibition ELISA method can be used for the protection detection of the grass carp interleukin 10. The detection range of the ELISA method is 0.1-100 ng / mL. By utilizing the polyclonal antibody and the competitive inhibition ELISA method, the cost is low, and the stability and the repeatability are good. The conventional method is that the competitive inhibition ELISA method is firstly established to detect protection expression of the grass carp interleukin 10.

The invention provides a compound WXSA-082B based on inhibiting histone demethylase, further provides a preparation method thereof. Tests shown that the compound can enable H3K4me3 protein level in human gastric carcinoma cell BGC-823 to increase obviously, has obvious RBP2 enzyme activity inhibiting effect, and can reduce the transfer ability of the human gastric carcinoma cell BGC-823. The compound provided by the invention can be applied to preparation of anti-gastric carcinoma drugs serving as a gastric carcinoma inhibitor. The structure of the compound is as follows: (the structure is shown in the description).

The invention discloses a compound B11 used as a histone methyltransferase NSD3 activity inhibitor and pharmaceutical application thereof. The compound has a chemical structure shown as a formula I: the formula I is shown in the following description; a chemical name is N-(1,3-dioxoisoindolin-4-yl)-4-phenoxybenzamide; the pharmaceutical application is that at least one of the compound B11 or hydrate thereof, pharmaceutically acceptable salts, a tautomer, a stereoisomer and a precursor compound is used as an active component to be used for preparing an anti-tumor medicine. The compound B11 provided by the invention can be used for effectively inhibiting the NSD3 enzymatic activity and an enzymology level IC50 value is 26.17+ / -4.75mu mol / L; the compound B11 has a good NSD3 enzymatic inhibition effect. The compound provided by the invention is used as an effective inhibitor of a tumor important target spot NSD3, is hopefully used as the active component to prepare the anti-tumor medicineand has a medicinal prospect.

The invention discloses application of a small molecule compound in anti-African swine fever virus ( ASFV) infection, and belongs to the technical field of medicine. According to the invention, an enzyme active center of E165R to exert hydrolytic action is defined by carrying out a crystal structure analysis of an E165R-dUMP complex, and then 1,2,3,4,6-O-Pentagalloylglucose capable of matching theE165R enzyme active center and significantly inhibiting E165R enzyme activity is obtained through in vitro screening by using the enzyme active center of E165R as a target. Further virus level experiments show that the 1,2,3,4,6-O-Pentagalloylglucose can significantly inhibit the replication of the ASFV in porcine alveolar macrophages, with high application value in clinical treatment or prevention of ASFV infection.