84 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.

The invention discloses a method for enhancing squalene synthesis through oil tea HMGR gene editing. According to the method, phosphorylation regulation and control sites Ser47 and / or Thr208 recognized by MAPK are targeted, and enzymatic activity inhibition is relieved and metabolic flux is enhanced by constructing phosphorylation resistance mutants (such as Ser-> Ala and Thr-> Val). The constructed editing vector can be introduced into camellia oleifera tissues in manners of PEG-mediated protoplast transient transfer, agrobacterium infection of calluses and the like, so that stable expression is realized. Experiments prove that the enzyme activity of HMGR in the editor is remarkably improved, the squalene accumulation amount is increased by 50% or above, the editing efficiency is high, expression is stable, and the method is suitable for high-value development of plant triterpenoid functional components and excellent strain breeding. The method also has the potential of popularization and application in other triterpenoid synthetic crops.

Disclosed herein are compounds used as inhibitors of KAT6 and pharmaceutical compositions comprising the compounds. Also disclosed are methods for treating a disorder or disease responsive to the inhibition of KAT6 activity in a subject. In an embodiment, the compounds are of formula (I) or a pharmaceutically acceptable salt thereof, or a deuterated analog thereof, or an N-oxide thereof, or a tautomer thereof, wherein values for the variables (e.g., ring B, A', A2, A3, A4, A5, Xl, L, R62, R63, R64, R7, and n) are disclosed herein.

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 application of long non-coding RNA Gm17586 in targeting SIRT1 to induce Smad3 acetylation and promote HSCs activation in liver fibrosis belongs to the field of research on the disease mechanism of liver fibrosis. The present invention establishes an in vitro HSCs cell model and determines that long non-coding RNA Gm17586 can target and regulate SIRT1 activity, inhibit Smad3 deacetylation modification, and then enhance Smad3 transcriptional activity, promote HSCs activation, and thus accelerate the occurrence and development of liver fibrosis through CCK8, RT-qPCR, WB, FISH, CO-IP, dual luciferase reporter gene experiments and other technologies.

The present invention provides a use of an inhibitor of fatty acid synthase (FASN) or its gene activity in the preparation of a drug for treating essential thrombocythemia (ET). The inventors have verified that the FASN small molecule inhibitor and the BASIN The therapeutic effects of gene editors or inhibitory nucleic acids in ET in vitro and in vivo models were evaluated, and the possibility of FASN or its gene as a new target for ET treatment was evaluated, providing new ideas for the clinical treatment of ET.

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.

Provided is a lipase for which activity inhibition by surfactants is reduced and which exhibits a high cleaning effect. A lipase consisting of the amino acid sequence of SEQ ID NO: 14 or an amino acid sequence having at least 91% identity thereto.

Provided in the present invention are a PKMYT1 inhibitor compound as represented by structural formula (I), a prodrug, an optical isomer, a tautomer, an isotope derivative, a solvate, a pharmaceutically acceptable salt and a pharmaceutical composition thereof, and a preparation method therefor and the use thereof. In the present invention, the high efficiency, safety, and feasibility of the compound of the present invention in targeted treatment are demonstrated by means of multi-dimensional validation of enzyme activity inhibition, cytotoxicity, safety and in-vivo efficacy. Moreover, the compound of the present invention has a very strong PKMYT1 inhibitory effect, and thus can be used as a drug for treating diseases associated with PKMYT1 overexpression.

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.

This invention relates to the field of pharmaceutical preparation technology, and more particularly to the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or drugs with lipase activity inhibition. This invention provides the application of purcanapeptide in the preparation of weight-loss and lipid-lowering drugs or drugs with lipase activity inhibition. This invention combines purcanapeptide with orlistat, achieving a synergistic effect between the two components. Furthermore, this invention fully considers the composition of the raw materials and the ratio between them, enabling the raw materials to work together in a specific ratio to exert a weight-loss effect.

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.

The present invention discloses a flavonoid derivative and a preparation method and application thereof, relating to the technical field of pharmaceutical chemistry. The flavonoid derivative comprises a chrysin derivative or a baicalein derivative. The general structural formula of the chrysin derivative is shown in Formula I-1, and the general structural formula of the baicalein derivative is shown in Formula I-2. The results show that the compound 2-phenyl-5-hydroxy-7-((6-(4-methoxypiperidine-1)-2-methylpyrimidin-4-yl))oxy)-4H-chromene-4-one (BY6) has significant cytotoxic activity (IC) against A549 cell lines. 50 :14.70μM), with higher inhibitory activity than cisplatin; and the best cytotoxic activity against PC‑3 cell line (IC 50 :9.18μM), and its inhibitory activity was comparable to that of cisplatin; its inhibitory activity against HCT116 cell line was comparable to that of cisplatin (IC 50 :19.47 μM).

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: