19 results about "Competitive inhibitor" patented technology

This invention belongs to the field of biomedical technology and provides a polypeptide with ATG8 protein binding activity, comprising the following structure: X1-X2-X3-X4-X5-X6-X7; wherein: X1, X2, and X3 are independently selected from glutamic acid or are absent; X4 is selected from tryptophan, phenylalanine, or leucine; X5 is valine; X6 is selected from leucine, isoleucine, or valine; and X7 is selected from valine, tryptophan, phenylalanine, or tyrosine. Compared with existing autophagy inhibitors, this polypeptide has the following superior pharmacokinetic potential and development flexibility in terms of target selection, binding strength, and mechanism of action: the short sequence not only reduces synthesis costs but also leaves more room for modification, which is expected to significantly improve the metabolic stability and drug-likeness potential of the polypeptide; it can serve as a highly efficient ATG8 targeting ligand and can be widely used in the construction of biochemical probes, screening of PPI competitive inhibitors, and the development of targeted delivery systems.

The present invention belongs to the field of pharmaceutical synthesis and specifically discloses an L-phenylalanine derivative tyrosinase inhibitor and its preparation method. The tyrosinase inhibitor comprises a compound represented by formula (I) or a pharmaceutically acceptable salt, ester, stereoisomer, solvate, prodrug, or isotopic variant thereof. The compound represented by formula (I) of the present invention has tyrosinase inhibitory activity superior to that of kojic acid, can inhibit excessive melanin accumulation, and has great application potential in inhibiting mushroom tyrosinase. Therefore, it can be used as a mushroom preservative. The compound represented by formula (I) of the present invention exerts tyrosinase inhibitory activity by acting on amino acid residues and copper ions within the active site and is a reversible competitive inhibitor. #imgabs0#

The invention discloses the technical field of biological medicine, and particularly relates to application of caffeic acid phenethyl ester in preparation of a ribosome large subunit protein L1 targeted inhibitor. According to the present invention, the drug affinity induced target stability discovers that the ribosome large subunit protein L1 target inhibitor can directly target the ribosome large subunit protein L1 in bacteria, and can be adopted as the competitive inhibitor to competitively combine with the RRF L1 so as to inhibit the ribosome recovery process, such that the bacterial translation process is inhibited, and the bacterial protein synthesis blocking and death are caused. The mechanism enables the ribosome large subunit protein L1 to become a ribosome target with therapeutic potential, provides a new target and theoretical basis for clinical treatment of bacterial infection, and provides new support for screening of new broad-spectrum antibiotics.

The present disclosure relates to the use of competitive inhibitors of the CCR5 receptor, such as the monoclonal antibody leronlimab, or binding fragments thereof, in the treatment or prevention of cancer.

The invention discloses a compound and application thereof. The invention provides a series of novel compounds with chemical structures reported for the first time. An activity research result shows that the series of novel compounds can competitively inhibit the combination of a natural substrate simulant of an SH2 substructural domain in a Cbl-b TKB structural domain and the SH2 substructural domain in the Cbl-b TKB structural domain. The competitive inhibition effect of the series of novel compounds can reduce the function of the Cbl-b protein, so that the continuous activation of T cells can be caused, and the tumor removal capability mediated by the T cells can be enhanced. Therefore, the series of novel compounds have the prospect of being developed into antitumor drugs. In addition, the series of novel compounds can also be developed into a reagent which is competitively combined with the SH2 substructural domain in the Cbl-b TKB structural domain, and the effect of the reagent includes but is not limited to a competitive inhibitor reference substance of the SH2 substructural domain in the Cbl-b TKB structural domain.

The application discloses application of aurantiamarin in preparation of a GLUT1 protein targeting inhibitor with high affinity, and belongs to the technical field of medicinal chemistry. It is found that aurantiamarin shows micromolar (muM) level high-efficiency inhibitory activity on GLUT1, and the aurantiamarin may play a role through a new mechanism different from existing competitive inhibitors, such as allosteric inhibition or state-dependent blockage, effectively blocks glucose uptake, and is not prone to drug resistance.

Disclosed herein are high-throughput synthetic methods for deliberately and prospectively discovering molecular glues that can be used to form complex protein-ligand surfaces that facilitate interfacial binding to other proteins on a dispersed surface. Specifically, the present application discloses a high-throughput method that uses sulfur(VI) fluoride exchange (SuFEx) transformation and N-hydroxysuccinimide (NHS)-ester derivatized amide coupling to prospectively repurpose known ligands of a protein of interest as degraders and compounds capable of inducing proximity to other proteins. Disclosed herein are methods of developing known ligands of a target protein into degraders of the target protein. Also disclosed are methods of developing a novel small molecule chromatin-competitive inhibitor of the 11-19 Leukemia (ENL) YEATS domain into an effective degrader of ENL.

To provide a combination therapy for use in treating hormone receptor positive and HER2 negative locally advanced unresectable or metastatic breast cancer.SOLUTION: Provided is a method comprising administering a combination therapy including ipatasertib, fulvestrant, and a CDK4 / 6 inhibitor over a 28-day cycle.SELECTED DRAWING: Figure 1A

The invention discloses an application of a compound 653-47 hydrochloride in preparation of a medicine for treating cerebral arterial thrombosis. The compound 653-47 hydrochloride or N2-(((9H-fluoro-9-yl) methoxyl) carbonyl)-N5, N5-dimethyl-L-glutamine can be applied to preparation of a medicine for treating cerebral apoplexy, a medicine for inhibiting inflammatory response, a medicine or reagent for inhibiting combination and interaction of TNFRSF14 protein and LIGHT protein, a competitive inhibitor of the TNFRSF14 protein and the like. Based on an astrocyte line of stable overexpression TNFRSF14 protein, it is clear that 653-47 hydrochloride treatment can significantly inhibit TNFRSF14-LIGHT interaction for the first time, then inflammatory response is inhibited, and a new potential therapeutic drug is provided for treatment of cerebral arterial thrombosis.

This invention discloses the application of tauroursodeoxycholic acid (TUDCA) in inhibiting α-glucosidase activity, belonging to the field of biotechnology. The invention utilizes porcine bile salts and bear bile powder for in vitro α-glucosidase inhibition experiments, performs molecular docking simulations on the components, and screens multiple bile acids for α-glucosidase inhibition, ultimately identifying TUDCA as the experimental material. Furthermore, in vivo and in vitro experiments were conducted to study the effects of TUDCA on α-glucosidase, revealing that TUDCA can significantly inhibit α-glucosidase activity and alleviate insulin resistance, classifying it as an anti-competitive inhibitor. This invention provides a novel raw material for inhibiting α-glucosidase activity, which can be applied to α-glucosidase activity inhibitors or drugs for alleviating insulin resistance.

The application discloses a SP10 / ACP / PSA triple detection test strip and a preparation process thereof, wherein a nitrocellulose membrane in the test strip is provided with a first detection line T1, a second detection line T2, a third detection line T3 and a quality control line C; the first detection line T1 is marked with SP10 monoclonal antibody 1; the second detection line T2 is marked with ACP monoclonal antibody 1; the third detection line T3 is marked with PSA monoclonal antibody 1; the quality control line C is marked with avidin SA; and the combination pad is provided with quantum dot microspheres marked with SP10 monoclonal antibody 2, ACP monoclonal antibody 2 and PSA monoclonal antibody 2; the test strip can simultaneously detect three indexes, and has simple product structure and convenient operation; the marking process in the preparation process adopts a competitive inhibitor and a quencher, solves the hook effect, and simultaneously obviously improves the specificity of each index.

Bifunctional compounds comprising a GDC-0068 analog that binds AKT isoforms AKT1, 2 and 3 and a degron which represents a moiety that binds an E3 ubiquitin ligase, covalently attached to each other by a linker, pharmaceutical compositions, and methods for treating diseases or conditions mediated by dysfunctional AKT activity.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a GCN2 kinase inhibitor in preparation of a medicine for treating alcoholic liver diseases. The GCN2 kinase inhibitor is an ATP (adenosine triphosphate) competitive inhibitor GCN2iB-1; the chemical formula of the GCN2iB-1 is C18H12ClF2N5O3S, and the inhibitor shows a remarkable treatment effect in a disease model by efficiently inhibiting the activity of GCN kinase: the inhibitor can effectively reduce liver lipid deposition, improve liver function indexes and dyslipidemia and relieve oxidative stress and inflammatory response. Experimental results show that the inhibitor has a definite treatment effect, and no obvious toxic or side effect is observed. The invention provides a new target spot and an effective candidate medicine scheme for treating the alcoholic fatty liver.

The present invention discloses a method for screening plant active substances that inhibit methane production in ruminants and its application. The method takes methyl-coenzyme M reductase (MCR protease) of ruminant gastrointestinal microorganisms as the target, and based on high-throughput virtual screening technology, combined with the design ideas of competitive inhibitors of protease substrates COB and COM, screens out two types of plant active substance sets with similar binding properties to MCR-COB and MCR-COM, respectively, and with methane production inhibition potential. In vitro experiments show that the traditional Chinese medicines corresponding to the screened plant active substances with similar binding properties to the methyl-coenzyme M reductase substrate COB have higher methane production inhibition effects, especially the inhibitory effects of three traditional Chinese medicine ethanol extracts on rumen methane production are greater than 65%. The present invention provides a method for quickly and efficiently screening plant active substances that inhibit methane production in ruminants, and the three traditional Chinese medicine ethanol extracts obtained by this method have good application prospects in animal husbandry production.

A method is provided for treating chronic myeloid leukemia in chronic phase and / or accelerated phase and / or blast phase, and / or acute lymphoblastic leukemia in a subject by administering to the subject a compound of formula (I) or a pharmaceutically acceptable salt, crystalline form, solvate, or hydrate thereof. The use of the compound of formula (I) or the pharmaceutically acceptable salt, crystal, solvate, or hydrate thereof in combination with an ATP-competitive BCR-ABL1 inhibitor is also provided. (I)

The application belongs to the technical field of biological medicine, and particularly relates to application of a GCN2 kinase inhibitor in preparation of a medicine for treating alcoholic liver disease. The GCN2 kinase inhibitor is an ATP competitive inhibitor GCN2iB-1; the chemical formula of the GCN2iB-1 is C 18 H 12 ClF2N5O3S, the inhibitor can effectively inhibit the activity of GCN kinase, and exhibits significant therapeutic effect in a disease model: can effectively reduce liver lipid deposition, improve liver function indexes and dyslipidemia, and relieve oxidative stress and inflammatory response. Experimental results show that the inhibitor has clear treatment effect, and no obvious toxic side effects are observed. The application provides a new target and an effective candidate drug scheme for treatment of alcoholic fatty liver.

The present application relates to the technical field of biomedicine, and particularly relates to a competitive inhibitor and application thereof, the competitive inhibitor can specifically bind to PGK1, and has a competitive inhibition effect on the combination of PGK1 and PD-1. The present application finds a new mechanism of PGK1 in mediating the activation of PD-1 without relying on the extracellular ligand of PD-1. The competitive inhibitor can directly target PGK1, and block the interaction between PGK1 and PD-1, so as to avoid the activation of PD-1 by PGK1 as much as possible. The competitive inhibitor provided by the present application has a promising prospect as an effective solution to the problem of PD-1 monoclonal antibody resistance.

This invention discloses a selenium-enriched walnut protein angiotensin-converting enzyme (ACE) inhibitory peptide, its preparation method, and its applications. The peptide SeMYHAN (682.1934 Da) provided by this invention forms 10 hydrogen bonds with 8 amino acid residues on ACE and may act as a non-competitive inhibitor binding to ACE (IC50). 50 =0.123 mg / mL). Furthermore, SeMYHAN increased NO release and decreased intracellular ET-1 expression in EA.hy926 cells, validating its antihypertensive effect at the cellular level. In conclusion, the selenium-enriched walnut ACE inhibitory peptide SeMYHAN shows promise as a good antihypertensive drug, and also provides a new theoretical basis for the high-value utilization of natural organic selenium.

The invention relates to the technical field of plant distant hybridization, and discloses a tulip trans-genus hybridization method, which comprises the following steps: firstly, coating a female parent tulip stigma with a first chemical composition containing a specific competitive inhibitor and a nano beacon, the composition being used for constructing a bionic affinity environment to overcome pre-fertilization obstacles, and implanting a space marker at a target site; then pollinating the pollen of the heterogeneity male parent to the pollen of the heterogeneity male parent; and finally, injecting a second chemical composition into the female parent daughter room at a specific time after pollination. The second chemical composition comprises a targeting nano-carrier of which the surface is modified with a docking ligand, and the carrier has a multi-layer core-shell structure, so that programmed release of active substances required in different development stages can be realized. By means of the established positioning targeting programmed release collaborative system, reproduction isolation recognition of female parents can be actively closed, meanwhile, precise targeting and dynamic nutrition support are conducted on successfully fertilized hybrid embryos, and the problems of incompatibility before fertilization and embryo abortion after fertilization are solved.