642 results about "Enzyme inhibitor" patented technology

In a small molecule drug discovery method, a transition state for a specific enzyme is modelled using quantum mechanics and molecular dynamics based simulation of the enzyme and substrate reaction; data defining the transition state (a ‘quantum pharmacophore’) is fed to a machine learning engine configured to generate transition state analogues, such as enzyme inhibitors.

An α-amylase inhibitory peptide. The peptide comprises amino acid sequences of eight adjacent amino acids X1, X2, X3, X4, X5, X6, X7, and X8, wherein each amino acid of the peptide is independently selected from a D-amino acid or an L-amino acid, and at least one of X2, X4, and X6 is W. The peptide has α-amylase inhibitory activity, has the effects of losing weight and lowering blood sugar, and can be used for preparing α-amylase inhibitors, weight-losing drugs, hypoglycemic drugs, or foods, health-care products or drugs for preventing or treating obesity-related diseases.

Provided herein are certain fused ring compounds, such as a compound of Formula (A), as Werner Syndrome RecQ DNA helicase (WRN) inhibitors, pharmaceutical compositions comprising the compounds, and method of use of the compounds or pharmaceutical compositions in the treatment of diseases or disorders.

The invention discloses a tyrosinase inhibitory peptide from kelp as well as a preparation method and application of the tyrosinase inhibitory peptide. The preparation method comprises the following steps: pretreating kelp, fermenting the kelp by using lactobacillus plantarum, carrying out centrifugation, ultrafiltration and component identification on the obtained fermentation liquor to obtain the composition of kelp polypeptide, screening the tyrosinase inhibitory peptide through molecular docking, and finally carrying out solid-phase synthesis to obtain the tyrosinase inhibitory peptide prepared by the invention. The lactobacillus plantarum fermentation technology is simple and feasible, the production cost is low, equipment is easy to obtain, active ingredients in kelp can be released to the maximum extent, and the prepared polypeptide has the effect of inhibiting the activity of tyrosinase and can be used for developing a tyrosinase inhibitor.

Disclosed is a series of pyrazolopyridine compounds, and application thereof in the preparation of RET kinase inhibitors for treatment. Specifically disclosed is the compound represented by formula (I), or a pharmaceutically acceptable salt thereof.

Compounds of formula (I)wherein A, R, W, Q, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.

The invention discloses application of a lysosome cathepsin L inhibitor in a medicine for treating or relieving allergic airway inflammation, and relates to the field of allergic airway inflammation. It is found through research that inflammatory response of asthma can be relieved by inhibiting expression of lysosome CTSL in macrophages and animal models; the inflammatory response of asthma can be relieved by inhibiting expression of lysosome CTSL in macrophages by using a small-molecule inhibitor and myeloid specific knockout CTSL, so that the lysosome cathepsin L inhibitor can effectively relieve allergic airway inflammation, and a new direction can be provided for research and development of drugs for treating and relieving allergic airway inflammation in the future.

The invention provides an application of atractylis lactone as a beta-glucuronidase inhibitor. Experiments find that atractylenolide can act on active sites of beta-glucuronidase to generate various bonding effects and play an inhibition role, and atractylenolide shows a dose-dependent relationship on activity inhibition of beta-glucuronidase. Furthermore, the atractylenolide can be used as a beta-glucuronidase inhibitor for preventing and treating related diseases (such as drug-induced diarrhea, diabetes mellitus, calculus and the like), and has very good research and application values.

The invention discloses a preparation method of deer spleen aminopeptide powder in the field of bioactive substance extraction and functional material compositing, and the performance of the deer spleen aminopeptide powder is improved by compositing a multi-stage functional modified material and deer spleen aminopeptide. The preparation method comprises the following steps: cleaning, homogenizing and crushing fresh deer spleen, extracting with a phosphate buffer solution, adjusting the pH value, carrying out enzymolysis, inactivating enzyme, and treating with an ultrafiltration membrane and a nanofiltration membrane in a specific molecular weight range to obtain a concentrated solution; and mixing the concentrated solution with a multi-stage functional modified material under proper conditions, sterilizing, pre-freezing, and freeze-drying to obtain the deer spleen aminopeptide powder. Wherein the modified material is constructed through quaternization modification, nanopore loading, enzyme inhibitor coupling and targeting ligand modification, and has the functions of charge repulsion, steric hindrance, enzyme inhibition and targeting recognition. The deer spleen aminopeptide powder prepared by the invention has high stability and good bioavailability, and is suitable for functional food or health care products.

The invention relates to the technical field of plant tissue extraction, in particular to an efficient extraction method and application of ginseng callus-derived exosomes, the extraction method comprises the following steps: S1, mixing ginseng callus with a PBS buffer solution, homogenizing and filtering to obtain a filtrate; s2, adding a protease inhibitor and a deep eutectic solvent into the filtrate, uniformly mixing, and standing to obtain a mixed solution; s3, centrifuging and filtering the mixed solution, and reserving supernate; s4, carrying out ultracentrifugation on the supernatant, collecting the precipitate, and resuspending with PBS to obtain a resuspension; and S5, further filtering the resuspension to obtain a filtrate, and storing at low temperature. The ginseng callus exosome extracted by the extraction method disclosed by the invention can be applied to preparation of drugs or cosmetics with anti-oxidation, anti-inflammatory and anti-aging effects, and the technical problems of low extraction efficiency, insufficient purity, complex extraction operation and poor stability of the extracted exosome in the existing exosome extraction technology can be effectively solved.

The invention discloses a rice ACCase mutant protein and a preparation method thereof. The amino acid sequence of the ACCase mutant gene encoding protein has the following mutations: the 2052nd site corresponding to the amino acid sequence of wild rice ACCase is mutated, isoleucine (I) is changed into asparagine (N), or isoleucine (I) is changed into glutamine (Q), or isoleucine (I) is changed into cysteine (C), or isoleucine (I) is changed into cysteine (C), or isoleucine (I) is changed into cysteine (C), or isoleucine (I) is changed into cysteine (C), or isoleucine (I) is changed into cysteine (C). And the plant can have extremely strong resistance (tolerance) to acetyl-coenzyme A carboxylase inhibitor herbicides. After the rice containing the rice ACCase mutant protein disclosed by the invention is applied with an acetyl-coenzyme A carboxylase inhibitor herbicide with 8 times of recommended use concentration, plants still grow normally, and the tolerance of the herbicide is greatly enhanced, so that the rice ACCase mutant protein can be widely applied to breeding of herbicide-resistant plants.

The invention discloses a CRISPR (clustered regularly interspaced short palindromic repeats)-Cas system-combined high-sensitivity DNA (deoxyribonucleic acid) methyltransferase activity determination system and a CRISPR-Cas system-combined high-sensitivity DNA methyltransferase activity determination method. DNA tetrahedrons capable of forming dumbbell rings at four corners are designed, when Dam MTase exists, Dam methyltransferase modifies an adenine residue in a GATC sequence, the adenine residue is subjected to Dpn I recognition and shearing and then is combined with a CRISPR / Cas 12a system, and only when a recognition site is methylated, the Dam methyltransferase can be used for detecting the activity of the GATC sequence. Only when the DpnI identifies the site and cuts the site, the exposed single chain can be combined with a CRISPR / Cas system to generate an enzyme digestion effect, the fluorescent single chain is cut and cut to generate fluorescence, and the concentration of Dam MTase can be known according to the size of the fluorescence. Certain clinical significance is realized when the kit is applied to early diagnosis of diseases such as cancers.

The invention provides inter alia methods of treating cancer comprising administering to a subject a cytidine triphosphate synthase 1 (CTPS1) inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor.

The invention provides an angiotensin converting enzyme inhibitory peptide and application thereof. The amino acid sequence of the angiotensin converting enzyme inhibitory peptide is PVKP. The ACE inhibitory activity of the inhibitory peptide PVKP provided by the invention is obviously improved compared with that of the original inhibitory peptide LYPVK, and the IC50 value is reduced from 10.6 mu g / mL to 9.6 mu g / mL; the digestive enzyme stability of the inhibitory peptide PVKP provided by the invention and the digestive enzyme stability of the original inhibitory peptide LYPVK under the same concentration are improved. Molecular simulation docking verifies that the interaction force between the ACE inhibitory peptide PVKP and ACE is enhanced compared with that of an original inhibitory peptide LYPVK, and the interaction force between alkyl groups and the interaction between the alkyl groups and Zn < 2 + > of an ACE active center are increased. The intracellular antihypertensive activity of the ACE inhibitory peptide PVKP is further verified through cell experiments, and compared with the original inhibitory peptide LYPVK, the intracellular NO release content is increased, and the ET-1 content is reduced. The ACE inhibitory peptide PVKP is small in molecular weight and good in water solubility, and application of the ACE inhibitory peptide PVKP in development of products with the blood pressure lowering effect is facilitated.

The present invention relates to an inhibitory polypeptide for use in treating and / or preventing a transmembrane serine protease (TMPRSS) and / or neutrophil elastase mediated disease in a subject, wherein said inhibitory polypeptide comprises an amino acid sequence of SEQ ID NO:1 or an amino acid sequence at least 70% identical thereto. The present invention further relates to polynucleotides, host cells, devices, kits, and uses related thereto.

The invention relates to the field of cell biology, and particularly discloses a neural stem cell induced differentiation culture medium and application thereof in preparation of neural stem cells. The neural stem cell induced differentiation culture medium is composed of a basic culture medium and additives, wherein the additives are composed of an N-2 additive, a B-27 additive, glutamine, a human leukemia inhibiting factor, a GSK-3 inhibitor, an ALK inhibitor, a gamma-secretase inhibitor and a CDK8 inhibitor. The neural stem cell induced differentiation culture medium is clear and simple in component, does not need to use antibiotics, and does not contain animal-derived components. When the culture medium is used for carrying out differentiation induction on the human pluripotent stem cells, the human pluripotent stem cells can be induced and differentiated into the neural stem cells within a short time (6-7 days) without depending on pluripotent stem cell cloning and a single cell state, the nonuniformity of pluripotent stem cell cloning formation can be overcome, and the purity of the neural stem cells is improved.

The invention discloses preparation of immobilized alpha-glucosidase based on a magnetic metal organic framework (MOF) and application of the immobilized alpha-glucosidase in screening of natural enzyme inhibitors. According to the method, ZIF-90 is grafted on the surfaces of Fe3O4 magnetic nanoparticles modified by codeposition of polydopamine and polyethyleneimine, and alpha-glucosidase is synchronously encapsulated in situ in the growth process of the ZIF-90, so that the magnetic MOF immobilized alpha-glucosidase is successfully constructed. On the application level, an in-vitro enzyme inhibition activity evaluation system is constructed, multiple traditional Chinese medicine extracts are selected as research objects, and by means of the characteristic that the magnetic MOF immobilized alpha-glucosidase is easily separated from a reaction system, accurate screening of natural inhibitors or active small molecules is rapidly and efficiently achieved; and a novel screening method is provided for research and development of candidate drugs for diabetes mellitus. The method comprises the following steps: 1, preparing the magnetic MOF immobilized alpha-glucosidase and evaluating the performance of the magnetic MOF immobilized alpha-glucosidase; and 2, the prepared immobilized alpha-glucosidase is used for screening a natural enzyme inhibitor. Based on a magnetic MOF immobilized enzyme technology, the method provided by the invention has the characteristics of rapidness, high efficiency, accuracy, easiness in separation from a reaction system and reutilization of a target receptor alpha-glucosidase, is suitable for screening of alpha-glucosidase inhibitors in complex systems such as traditional Chinese medicines, and has a wide application prospect.

Provided herein are certain aminoheteroaryl compounds with tricyclic structure moiety, pharmaceutical compositions, and methods of use related to cyclin dependent kinases (CDKs). The compounds provided herein are typically CDK4 inhibitors, which can be used for treating a variety of diseases or disorders, such as cancer.

The invention provides a plant cytosine single-base editor as well as a construction method and application thereof, and relates to the technical field of plant genetic engineering. The single-base editor provided by the invention is named as hyPopCBE, and has a structural formula shown in the description, the editor comprises hA3A / Y130F cytosine deaminase, an optimized human-derived Rab51 single-stranded DNA binding protein structural domain, a fusion protein of nCas9 nuclease and a uracil glycosylase inhibitor, a fusion protein expression unit of phage MS2 coat protein and the uracil glycosylase inhibitor, and a guide RNA transcription expression unit integrated with an MS2 binding sequence. Compared with an existing plant cytosine single-base editor, the single-base editor constructed by the method can remarkably improve the editing efficiency of plant alleles, and the stability is higher; when the herbicide-resistant poplar gene is applied to poplar, a new herbicide-resistant poplar germplasm can be successfully created, and a technical support is provided for research and molecular breeding of a poplar functional genome.

The invention discloses a tyrosinase inhibitor, a preparation method thereof and application of the tyrosinase inhibitor in preparation of a product for inhibiting tyrosinase activity. Based on the protein structure of the TYR, the TYR inhibitor which is novel in structure and higher in curative effect and selectivity is found by adopting reasonable drug design and structural modification strategies.

The invention discloses a small molecule peptide with xanthine oxidase inhibitory activity and application thereof, and belongs to the technical field of bioactive peptides. The amino acid sequence of the small molecule peptide with xanthine oxidase inhibitory activity is YDWRPF, and is as shown in SEQ ID NO. 8. The small molecule peptide with the xanthine oxidase inhibitory activity is applied to preparation of a xanthine oxidase inhibitor. The small molecule peptide YDWRPF is high in xanthine oxidase inhibitory activity, IC50 is only 2.73 + / -0.20 mM, and the small molecule peptide YDWRPF can be used as a raw material to prepare a xanthine oxidase inhibitor. The invention is of great significance to the treatment of hyperuricemia.

The present invention belongs to the technical field of genetic engineering. Provided are a single-base editor, a deaminase used therein, and the use thereof. The technical problems to be solved are to identify a naturally occurring cytosine deaminase without sequence preference, construct a base editor, and improve the efficiency and scope of base editing. In order to solve the technical problems above, a cytosine base editor is provided. The cytosine base editor is a fusion protein, wherein the fusion protein is a protein containing a cytidine deaminase, a Cas protein and a uracil-DNA glycosylase inhibitor, and the cytidine deaminase is a protein having an amino acid sequence of positions 28-164 of SEQ ID NO. 2. Further provided is the use of the fusion protein above and a biomaterial related thereto in plant single-base editing. The single-base editor can improve the efficiency of cytosine base editing and accurately mediate the base mutation of a target, and is widely applicable in the cells of maize and even other plants.

The invention belongs to the technical field of food additives and new materials, and discloses a thermostable embedding method and application of an alpha-amylase inhibitor, and the method comprises the following steps: respectively adjusting the pH values of an alpha-AL stock solution and an iota-CG stock solution to 6, then mixing the stock solutions according to the mass ratio of alpha-AL to iota-CG of 2: 1, and carrying out heat preservation for 2-3 hours, so as to obtain the thermostable embedding method of the alpha-amylase inhibitor. According to the method disclosed by the invention, the stable ion compound is formed under the condition that the pH is equal to 6 by utilizing the electrostatic interaction and the hydrogen-bond interaction between the negatively charged sulfuric acid group in the iota-carrageenan molecule and the positively charged amino acid residue on the surface of the white kidney bean alpha-amylase inhibitor. According to the compound, stable combination among molecules is achieved by constructing a structured water molecular layer barrier, so that the tolerance of the white kidney bean alpha-amylase inhibitor to heat treatment is remarkably improved, and the defect that the heat stability of the white kidney bean alpha-amylase inhibitor is poor is overcome.

The invention belongs to the field of medical chemistry, and particularly discloses a protein tyrosine phosphatase inhibitor, such as type 2 non-receptor protein tyrosine phosphatase (PTPN2) and / or type 1 non-receptor protein tyrosine phosphatase (PTPN1) inhibitor, a pharmaceutical composition and application thereof. The invention discloses a method for treating related diseases such as cancers and metabolic diseases by using the protein tyrosine phosphatase inhibitor.

The present invention provides use of a C-JUN N-terminal kinase inhibitor, SU3327, in the preparation of a medicament for enhancing the efficacy of polymyxin against bacterial infection, and use of a composition of SU3327 and polymyxin in the preparation of a medicament for an enhanced efficacy against bacterial infection, wherein the polymyxin is preferably Polymyxin E. The invention not only shows an enhanced antibacterial activity of polymyxin by SU3327 in synergy through minimum inhibitory concentration tests in checkerboard assays and in vitro bacterial growth curves, but also confirms the ability of SU3327 to enhance polymyxin along with its effectiveness in vivo in the experiments with a model of mice infected with drug resistant bacteria at the animal level. The invention provides a new use of SU3327 in enhancing antibacterial activities of polymyxin antibiotics, resolving the technical problems such as clinical resistance to polymyxin, low clinical therapeutic index of polymyxin, etc.

The invention discloses a single-base editor, deaminase used by the single-base editor and application of the single-base editor, and belongs to the technical field of genetic engineering. The technical problems to be solved in the invention are as follows: natural cytosine deaminase without sequence preference is mined, a base editor is constructed, and the base editing efficiency and range are improved. In order to solve the technical problem, the application provides a cytosine base editor, the cytosine base editor is a fusion protein, the fusion protein is a protein containing cytidine deaminase, a Cas protein and a uracil glycosylase inhibitor, and the cytidine deaminase is a protein at the 28th-164th site of an amino acid sequence SEQ ID NO.2. The invention also provides application of the fusion protein and related biological materials thereof in plant single base editing. The single-base editor provided by the invention can improve the efficiency of cytosine base editing, can accurately mediate the base mutation of a target site, and can be widely applied to corn and even other plant cells.

The invention provides a series of GMPS enzyme inhibitors. The invention includes potent GMPS inhibitors that specifically and covalently bind to GMPS, exhibit broad anti-cancer activity, block the infection efficiency of viruses, and have the potentials to suppress undesired immune responses. These novel inhibitors of GMPS, and their derivatives, have tremendous potentials to be used as therapeutic agents for the treatment of cancers, viral infection and immune disorders.

Methods and compositions for treating pain are provided. Methods for treating pain include administering an effective amount of dextromethorphan or a pharmaceutically acceptable salt thereof in combination with a CYP2D6 enzyme inhibitor and a CYP3A4 enzyme inhibitor to a subject in need thereof. Compositions for treating pain that include dextromethorphan or a pharmaceutically acceptable salt thereof in combination with a CYP2D6 enzyme inhibitor and a CYP3A4 enzyme inhibitor are administered to a subject in need thereof.

The invention provides a method for detecting an anti-C1 esterase inhibitor neutralizing antibody in a biological sample, and the method mainly utilizes the characteristic that protein A resin is combined with an Fc segment of the antibody to capture the antibody (containing the anti-C1 esterase inhibitor neutralizing antibody), so that the C1 esterase inhibitor and complement component 1s (C1s) in the biological sample after thermal inactivation are removed; furthermore, an antibody (containing a neutralizing antibody) or an anti-C1 esterase inhibitor compound on the protein A resin is subjected to acid dissociation through an acidolysis solution, so that not only can the anti-C1 esterase inhibitor neutralizing antibody existing in a free form in a biological sample be detected, but also the anti-C1 esterase inhibitor neutralizing antibody existing in a combined form in the biological sample can be detected.

The invention discloses an anti-leaching nutrient slow-release synergistic compound fertilizer, and particularly discloses an anti-leaching nutrient slow-release synergistic compound fertilizer and a preparation method thereof. The compound fertilizer comprises the following components in parts by weight: 30-50 parts of urea particles, 15-25 parts of monoammonium phosphate, 20-30 parts of potassium sulfate, 2-5 parts of a slow-release synergistic coating agent, 1-3 parts of a bonding wrapping layer and 10-20 parts of a filling material. The slow-release synergistic coating agent comprises polyaspartic acid (PASP) and a composite inhibitor (a urease inhibitor and a nitrification inhibitor), and the bonding wrapping layer is made of a polyvinyl alcohol / sodium polyethylene acid-based cementing material. The preparation method comprises the following steps: mixing and granulating raw materials, carrying out primary coating (slow-release synergist), carrying out secondary coating (bonding a coating layer), and drying and screening. Through the synergistic effect of the double coating technology and the compound inhibitor, the nitrogen conversion and release are obviously delayed, the nutrient leaching loss is reduced by 20-40%, the fertilizer utilization rate is improved by 25-30%, and the compound fertilizer is suitable for high-temperature and rainy areas.