53 results about "Activity inhibition" patented technology

The invention discloses a hexapeptide with a hypoglycemic effect as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The amino acid sequence of the hexapeptide is Ile-Trp-Asp-Pro-His-Phe, and the amino acid sequence of the hexapeptide is as shown in the specification. The novel hexapeptide IWDPHF with prominent DPP-IV inhibition ability is successfully identified from mulberry leaf proteolysis products through liquid chromatography-mass spectrometry and a virtual screening method, the hexapeptide IWDPHF shows the blood glucose reducing effect superior to that of part of known peptides in an in-vitro enzyme activity inhibition experiment and a zebra fish hyperglycemia model, and no obvious side effect exists; the compound has a good potential of being developed into a hypoglycemic functional product or a drug lead compound. The invention further provides the mulberry leaf peptide with the peptide fragment IWDPHF, and the mulberry leaf peptide can be applied to preparation of drugs or food for reducing blood sugar. The invention provides a new scheme and theoretical basis for treatment of diabetes, and has good market prospect and application potential.

The invention relates to a pesticide residue detection test strip as well as a preparation method and application thereof, in particular to a rapid detection technology based on an enzyme inhibition method and a chitosan non-woven fabric carrier. The test strip can specifically detect organophosphorus and carbamate pesticides such as trichlorfon, malathion and phoxim through the enzyme activity inhibition principle, the detection limit of the pesticides such as phoxim is as low as 0.1 mg / kg, the developing intensity is in negative correlation with the pesticide concentration, and semi-quantitative judgment can be achieved. The preparation process is simple, the chitosan non-woven fabric is adopted as a fixed carrier, the material is environment-friendly and degradable, the enzyme activity recovery rate reaches 90%, the stability is excellent (the enzyme activity recovery rate can be preserved for 60 days at the temperature of 4 DEG C in a dark place), sample pretreatment is not needed in detection operation, a result can be obtained at the normal temperature for 15 min, the stability and repeatability are good, and the problems that a traditional instrument is high in detection cost and long in time consumption are solved; the method has a remarkable basic popularization value.

Provided is a lipase mutant with alleviated inhibition of activity against a dispersed substrate in the presence of a surfactant. The lipase mutant consists of an amino acid sequence having an identity of at least 75% with the amino acid sequence of SEQ ID NO: 2, 4, 6, or 8 and has a predetermined amino acid residue at a predetermined position numbered according to SEQ ID NO: 2.

The invention belongs to the field of biological medicine, and particularly relates to application of an active component based on a radish seed extract as an angiotensin converting enzyme inhibitor. The active ingredient is sinapine (sinapine) or nasturtoside (Gluconatutin), and the active ingredient is one or more than one of the active ingredients. According to the invention, affinity ultrafiltration is combined with a UPLC-Orbitrap-MS method, potential inhibitors are rapidly screened and identified on line from radish seeds, the affinity of active compounds and ACE is researched by combining molecular docking through ACE activity inhibition experiments, and finally two potential ACE inhibitors, namely sinapine and nasturtoside, are determined by combining an affinity ultrafiltration RBA value, IC50 and a binding force of molecular docking. And further research is carried out after screening, so that the research range is greatly reduced, the time of new drug discovery and research and development processes is saved, and the screening cost and risk are reduced.

The invention belongs to the technical field of drug screening, and particularly relates to an in-vitro high-throughput screening system of a PHD2 activity inhibitor and application of the in-vitro high-throughput screening system. The in-vitro high-throughput screening system for the PHD2 activity regulator comprises a pore plate, a small molecule reaction system, an FITC (fluorescein isothiocyanate) labeled peptide fragment and a VBC compound, wherein a GST-PHD2 protein is attached to the surface of an inner cavity of the pore plate; the sequence of the GST-PHD2 protein is shown as SEQ ID NO. 1, the small molecule reaction system contains Tris-HCl, alpha-ketoglutarate disodium and vitamin C, the sequence of the FITC labeled peptide fragment is shown as SEQ ID NO. 2, and the sequence of the VBC compound is shown as SEQ ID NO. 3. The in-vitro high-throughput screening system can sensitively, accurately and efficiently detect the inhibiting effect of small molecular compounds on PHD2 protein activity, and has important scientific value and application prospect.

Provided here are methods directed to the T cell receptor cloning of heat shock protein 60 (HSP60), the generation of HSP60-specific regulatory T cells (Tregs), and adoptive cell transfer of HSP60-specific Tregs for the treatment of autoimmune and other disorders. Methods of treatment also include administering a therapeutically effective amount of an inhibitor of expression or activity of nucleus accumbens-associated protein- 1 (NAC1) along with the HSP60-specific Tregs.

The invention relates to the field of protein, in particular to a milk-derived peptide APPSPIGVF with antihypertensive activity as well as a preparation method and application of the milk-derived peptide APPSPIGVF, and the amino acid sequence of the milk-derived peptide APPSPIGVF is Ala-Pro-Pro-Ser-Pro-Ile-Gly-Val-Phe. An angiotensin converting enzyme activity inhibition experiment, an alpha-amylase activity inhibition experiment and a dipeptidyl peptidase-4 activity inhibition experiment prove that the milk-derived peptide APPSPIGVF has very good functions of resisting hypertension and reducing blood sugar. The milk-derived peptide APPSPIGVF disclosed by the invention has an anti-hypertension capability, and can be used for remarkably inhibiting the activity of alpha-amylase and dipeptidyl peptidase-4, improving the capability of resisting chronic diseases such as hypertension and hyperglycemia of an organism, reducing the morbidity of the organism and improving the quality of life; the method has very important significance for developing food, health care products and medicines with the functions of resisting hypertension and reducing blood sugar.

The invention discloses a novel application of a pyrrolone benzenesulfonamide compound, the compound has obvious antiviral activity and low cytotoxicity, can be used as an allosteric inhibitor of coronavirus 3CL protease (3CLpro), and especially shows efficient inhibition capability on SARS-CoV-2 3CLpro. An enzyme activity test and molecular dynamics simulation result shows that the compound is combined with a 3CLpro allosteric site to induce the volume of a catalytic pocket to shrink, so that enzyme activity inhibition is realized, and the drug resistance risk caused by active site mutation is avoided. In-vitro antiviral experiments further show that the compound has a strong inhibition effect on SARS-CoV-2 wild type and various drug-resistant mutant strains (such as E166V and S144M), the EC50 value is as low as the nanomole level, the selection index is high, and the safety is good. Besides, based on the high conservative property of 3CLpro in different coronaviruses, the compound provided by the invention also shows inhibitory activity on other coronaviruses 3CLpro such as SARS-CoV, MERS-CoV and the like, and has broad-spectrum antiviral potential. The compound can be used for preparing medicines for preventing, relieving or treating related diseases caused by coronavirus infection, and has a good clinical application prospect.

The invention discloses a formula and application of a compound infertility agent containing clarithromycin and quinestrol and based on CYP enzyme activity inhibition. The clarithromycin composition comprises clarithromycin, quinestrol and baits. The CYP enzyme inhibitor and the endocrine sterilant are combined for use, so that the synergist can effectively inhibit the activity of CYP enzyme in tissues such as livers of rats, the metabolic clearance rate of the sterilant is remarkably reduced, and the oral bioavailability and the system exposure level of the sterilant are improved. Therefore, when the same infertility effect is achieved, the use dosage of the infertility agent can be greatly reduced, so that the cost is saved, and the environmental load is reduced; or under the same dosage, a more thorough and more lasting population sterility effect can be obtained, and the practicability and competitiveness of a pest mouse sterility control technology are greatly improved.

The invention discloses a hemolysin-like protease inhibition composition for regulating vaginal micro-ecological balance as well as a preparation method and application of the hemolysin-like protease inhibition composition. The hemolysin-like protease inhibition composition disclosed by the invention is prepared from 10 to 20 percent of lactobacillus fermentation liquor, 10 to 30 percent of phloretin, 10 to 30 percent of naringenin, 30 to 40 percent of quercetin and 5 to 10 percent of sodium hyaluronate. The preparation method comprises the following steps: dissolving phloretin, naringenin, quercetin and sodium hyaluronate in 50% butanediol in proportion, and ultrasonically mixing uniformly to obtain a mixed solution; and slowly adding the mixed solution into the lactic acid bacteria fermentation solution, and uniformly stirring to obtain the hemolysin-like protease inhibition composition. According to the invention, natural active components with a hemolysin-like protease inhibition effect are screened to construct a synergistic system with three mechanisms of acidification environment regulation, enzyme activity inhibition and barrier repair, so that hemolysin-like protease can be directly inhibited, and the effect of inhibiting the hemolysin-like protease can be achieved by adjusting the local pH value and the micro-ecological environment of the vagina. Propagation of pathogenic bacteria is inhibited, and growth of dominant flora such as lactobacillus is promoted.

The present application discloses novel substituted pyridazine compounds and analogs, their preparation, pharmaceutical compositions comprising them and their therapeutic use as medicaments for the treatment of diseases or conditions associated with modulation of cytokines such as IL-1 [beta] and IL-18, modulation of NLRP3, or inhibition of activation of NLRP3 or components related to inflammatory processes.

The invention provides a compound prediction method and device based on artificial intelligence and a medium, and the method comprises the steps: determining a structure information graph according to atomic information corresponding to each atom in a to-be-predicted compound and chemical bonds among a plurality of atoms with interaction force; according to the inter-node feature vector of any two nodes in the structure information graph and the query vector and the key vector corresponding to the two nodes, initial attention weights corresponding to the two nodes are determined; and determining a target attention weight vector corresponding to each node according to the attention range value corresponding to each node and the initial attention weights corresponding to every two nodes so as to obtain activity inhibition results of a plurality of key targets corresponding to the to-be-predicted compound, the interaction influence between each atom in the to-be-predicted compound and the atoms in the local range corresponding to the atom is analyzed, so that the determined activity inhibition result of the key target spot is more accurate, and the data processing amount is reduced.

This invention discloses an anti-tumor composition and its application, relating to the field of biomedical technology. The composition comprises an inhibitor of anti-immune checkpoints and an inhibitor of the expression and / or activity of the RBM10 gene. Research in this invention has found that reducing the expression level of the RBM10 gene in lung cancer cells using substances such as shRNA can significantly enhance the therapeutic effect of the anti-immune checkpoint inhibitor on a mouse model of lung cancer, effectively inhibiting tumor growth; further combination with Eubacterium hallii and / or Akkermansia muciniphila can also effectively enhance the inhibitory effect on tumor growth.

This TRPA1 activity inhibitor is characterized by containing glycyrrhizic acid or a salt thereof as an active ingredient. This TRPV1 activity inhibitor is characterized by containing glycyrrhizic acid or a salt thereof as an active ingredient. By using glycyrrhizic acid or a salt thereof as an active ingredient, a TRPA1 activity inhibitor and a TRPV1 activity inhibitor with excellent action and effect can be provided.

This invention provides a COX2 inhibitory peptide, a composition for inhibiting COX2, and its application, belonging to the field of bioactive peptide technology. The amino acid sequence of the COX2 inhibitory peptide of this invention includes RGPF, FPK, or NPW. Studies have found that COX2 inhibitory peptides with amino acid sequences such as RGPF, FPK, or NPW exhibit an IC50 (increase in activity) for inhibiting COX2 activity. 50 The values ​​were 360.17±32.60 μM, 640.33±10.29 μM, and 1100.90±89.93 μM, respectively, which can effectively inhibit the activity of COX2, thereby effectively preventing and / or treating inflammation and cancer caused by COX2, and also achieving antipyretic and analgesic effects. Meanwhile, the COX2 inhibitory peptide of this invention has the advantages of being safe, non-toxic, and highly water-soluble, providing a safe option for the clinical use of COX2 inhibitors.

The invention provides a compound which is a compound as shown in a formula I or a tautomer, a stereoisomer, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug of the compound as shown in the formula I. OXCT1 protein can be effectively combined, and the dual-enzyme activity inhibition effect is achieved. Specifically, the compound not only can inhibit the activity of ketolytic enzyme of OXCT1, but also can inhibit the activity of succinyltransferase of OXCT1. Therefore, the compound can effectively prevent and / or treat cancers highly expressing OXCT1.

The application discloses a phenolic compound resistant starch for efficiently regulating blood sugar, a preparation method and application thereof. The phenolic compound resistant starch has V6 and V7 polymorphic structures, good thermal stability, better enzyme resistance, enzyme activity inhibition and glucose transport inhibition capacity, and the preparation method has simple process operation. The functional resistant starch can be used for preparing various products with the functions of regulating postprandial blood sugar, preventing and improving diabetes and other related metabolic disorders / diseases.

This invention belongs to the field of biomedical technology, specifically relating to phosphodiesterase 2 (PDE2) activity inhibitors. Six PDE2 activity inhibitors were screened, providing six compounds: sanguisorbin, Picropodophyllol, aristolochic acid D, Malabaricone A, tetradehydropodophyllotoxin, and Roseoflavin. These compounds can be used to prepare PDE2 activity inhibitor drugs. Biological experimental methods were used to detect and verify the activity, resulting in effective PDE2 enzyme inhibitors. The IC50 level of these inhibitors was measured. 50 It exhibits good PDE2 enzyme inhibition effect.

The invention relates to application of a bacterial metabolite in preparation of a metallo-beta-lactamase inhibitor and a drug for improving the sensitivity of bacteria to antibiotics and a pharmaceutical composition, and belongs to the technical field of biological medicines. The bacterial metabolite is N-acetyl-L-methionine and / or methyl malonic acid. The NDM-5 protein is expressed, separated and purified through a genetic engineering means, and an enzyme activity inhibition test, an enzyme inhibition ratio and semi-inhibition concentration determination prove that bacterial metabolites, namely N-acetyl-L-methionine and methylmalonic acid, can inhibit the activity of NDM-5 enzyme in a dose-dependent manner. The invention also proves that the N-acetyl-L-methionine and the methylmalonic acid can recover the antibacterial activity of the meropenem to NDM-1, NDM-5 and NDM-9 positive drug-resistant bacteria and have wide application prospects in the aspect of treating drug-resistant bacteria infectious diseases through a checkerboard method for measuring the minimum inhibitory concentration, a time-sterilization curve method and the like.

This invention provides an N-aryl-N-arylpropynyl-arylacetamide compound and its pharmaceutical uses. The provided compounds include their prodrugs, tautomers, stereoisomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. The compounds of this invention can serve as the first covalent inhibitor of POLQ. In vitro enzyme activity inhibition studies show that the compounds of this invention have strong inhibitory effects on POLQ enzymes and can serve as promising compounds for the treatment of POLQ-mediated diseases. Further studies have shown that typical compounds I-1, I-13, and I-25 have considerably long-lasting inhibitory activity against POLQ enzymes and good cellular activity. The synthetic method of this invention is simple and convenient, facilitating large-scale industrial production and application. The general structural formula of this invention is shown in Formula I:

The invention provides a compound which is a compound as shown in a formula I or a tautomer, a stereoisomer, a hydrate, a solvate, a pharmaceutically acceptable salt or a prodrug of the compound as shown in the formula I. OXCT1 protein can be effectively combined, and the dual-enzyme activity inhibition effect is achieved. Specifically, the compound not only can inhibit the activity of ketolytic enzyme of OXCT1, but also can inhibit the activity of succinyltransferase of OXCT1. Therefore, the compound can effectively prevent and / or treat cancers highly expressing OXCT1.

The present invention provides a novel memory disorder ameliorating agent. A PKC [gamma] activity inhibitor is useful as an active ingredient of a dysmnesia ameliorating agent.

The invention discloses a DPP4 response type QC inhibitor, a targeted nano delivery system and a preparation method and application thereof, and relates to the field of medicinal chemistry and medicinal materials. The DPP4 response type QC inhibitor comprises a QC inhibitor and a DPP4 recognition peptide fragment, the structural general formula of the QC inhibitor is that the general formula of the DPP4 recognition peptide fragment is (Xaa-Pro) n or (Xaa-Ala) n, Xaa is any amino acid, and n is an integer of 1-5; the QC inhibitor and the DPP4 recognition peptide fragment are connected through amide condensation. The DPP4 response type QC inhibitor disclosed by the invention can be specifically cut at a pE-A beta deposition part rich in dipeptidyl peptidase 4 (DPP4) of a brain, and the active QC inhibitor is released; the prodrug form is retained in the DPP4-free region, and no or low QC inhibitory activity is achieved. Therefore, the DPP4 response type QC inhibitor can reduce the non-specific toxicity of the existing QC inhibitor.

The invention relates to the technical field of computational toxicology and bioinformatics, and discloses a signal channel function enrichment analysis method, system, equipment and medium based on a protein inhibition ratio, which learns an interaction relationship between an active / inactive inhibitor and a key protein of a target signal channel by training an inhibition probability prediction model. Further predicting the inhibition probability of the to-be-detected compound on the key protein, and converting the inhibition probability into log2 (1-inhibition probability) as a novel input index of function enrichment analysis. According to the method, quantitative and systematic analysis on the potential pathway effect of the compound can be realized under the condition of lacking omics data; the multi-target inhibition effect is effectively integrated, the defects of single-target research are overcome, massive inhibitor data in a public database are fully utilized, and the data utilization rate and the research efficiency are remarkably improved; the method is especially suitable for environmental pollutant toxicity mechanism evaluation and multi-target activity prediction and pathway mechanism analysis of candidate compounds in drug research and development.

The application discloses screening of hemostatic active components in Euphorbiaceae plants and application thereof, and based on ultrafiltration mass spectrometry technology and taking urokinase-type plasminogen activator as a key target enzyme, a hemostatic active component, breynol, of cyclopentanone isocoumarins in Euphorbiaceae plants is screened for the first time. The breynol shows strong specific binding to urokinase plasminogen activator, and the activity inhibition (IC 50 ) of the breynol to the urokinase plasminogen activator is 0.187±0.000 mM, which is superior to that of the positive control tranexamic acid (IC 50 =2.425±0.001 mM). The breynol is reported for the first time in the research of hemostatic activity of Euphorbiaceae plants, and can be used for preparation of daily or clinical hemostatic drugs.

The invention discloses application of OTUD4 as a pancreatic adenocarcinoma (PAAD) treatment target, and belongs to the field of biological medicine. A large number of experiments prove that OTUD4 is highly expressed in PAAD tissue and is related to poor prognosis. In mechanism, OTUD4 interacts with YAP protein, and multi-ubiquitination connected with K48 of YAP is reduced through the activity of ubiquitination enzyme of OTUD4, so that the YAP protein is stabilized, a Hippo / YAP signal axis is activated, and PAAD progress is promoted. The inhibition of OTUD4 can down-regulate the activity of YAP, inhibit the proliferation, migration and invasion of pancreatic cancer cells, and induce apoptosis. The invention provides application of an OTUD4 inhibitor in preparation of a medicine for treating pancreatic cancer and a related diagnosis and screening method.

The application relates to antimony nanopowder and a preparation method and application thereof, and belongs to the technical field of metal powder processing. The method comprises the following steps: dispersing antimony nanopowder in a solvent to obtain a dispersion liquid; mixing the dispersion liquid with 5-10 times the mass of nitrobenzene diazonium salt (p-NBD) of the antimony nanopowder, and then reacting under the condition of light irradiation at 0-4 DEG C for 30-60 h to obtain passivated antimony nanopowder. The diazonium chemical reaction forms a stable covalent bond on the surface of Sb NPs, and blocks the interaction with respiratory tract cells. Compared with the original Sb NPs group, the nitrobenzene diazonium salt modified Sb NPs can reverse the GPX4 activity inhibition effect, make the GPX4 protein expression up-regulated and restored to the level close to the control group, and lose the ability to induce cell ferroptosis, so that the lung toxicity problem of Sb NPs is solved from the ferroptosis mechanism level.

Provided is a lipase mutant in which the inhibition of activity against a dispersed substrate in the presence of a surfactant has been alleviated. The lipase mutant consists of an amino acid sequence having an identity of at least 75% with the amino acid sequence of SEQ ID NO: 2, 4, 6, or 8 and has an amino acid residue other than isoleucine at a position corresponding to position 44 numbered according to SEQ ID NO: 2.