31 results about "Competitive inhibitor" patented technology

The present invention addresses the problem of providing an improving agent for improving a stratum corneum barrier function without external replenishment with any moisturizing substance and a pharmaceutical composition containing said improving agent. The present invention provides: a stratum corneum barrier function improving agent which contains a glycolytic inhibitor as an active ingredient; the stratum corneum barrier function improving agent in which the glycolytic inhibitor is at least one selected from the group consisting of a glucose transporter inhibitor and a glucose competitive inhibitor; either of said stratum corneum barrier function improving agents having at least one selected from the group consisting of an inhibitory effect on the loss of skin moisture retention capacity and an inhibitory effect on skin permeability enhancement; and a pharmaceutical composition which contains any of said stratum corneum barrier function improving agents.

The invention discloses a nano antibody and a preparation method and application thereof, the nano antibody comprises a heavy chain variable region, the heavy chain variable region comprises CDR1, CDR2 and CDR3, and the amino acid sequence of the heavy chain variable region of the nano antibody comprises SEQ ID NO: 3. The nano antibody provided by the invention is determined as a competitive OTR inhibitor with extracellular treatment potential; in-vitro and in-vivo experiments prove that the nano antibody has a curative effect equivalent to that of atosiban which is widely used clinically, and a new direction is provided for developing effective anti-premature delivery medicines.

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 invention belongs to the field of medicine synthesis, and particularly discloses an L-phenylalanine derivative tyrosinase inhibitor and a preparation method thereof. The tyrosinase inhibitor comprises a compound shown in a formula (I) or pharmaceutically acceptable salt, ester, stereoisomer, solvate, prodrug or isotope variant thereof. The compound shown in the formula (I) has tyrosinase inhibitory activity superior to that of kojic acid, can play a role in inhibiting excessive accumulation of melanin, and has great application potential in inhibiting mushroom tyrosinase, so that the compound can be used as a mushroom preservative. According to the invention, the compound shown in the formula (I) exerts tyrosinase inhibitory activity through amino acid residues and copper ions acting on active sites, and is a reversible competitive inhibitor. # imgabs0 #

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 invention provides a low molecular weight ATP-competitive MPS1 inhibitor for use in the treatment of hepatocellular carcinoma (HCC).

Disclosed herein are high throughput synthetic methods for the deliberate and prospective discovery of molecular glues which can be used to form composite protein-ligand surfaces that facilitate interfacial binding to other proteins over dispersed surfaces. In particular, this application discloses a high throughput approach using sulfur(VI) fluoride exchange (SuFEx) transformations and N-hydroxysuccinimide (NHS)-ester derived amide couplings to prospectively repurpose known ligands for a prolein-of-interest into 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 proteins. Further disclosed are methods of developing novel small molecule chromatin-competitive inhibitors of the eleven nineteen leukemia (ENL) YEATS domain into effective degraders of ENL.

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.

The invention relates to the technical field of biology, in particular to a methionine tRNA synthetase inhibitor and application thereof. The inhibitor is isoconic acid and a derivative thereof; the invention finds that isoconic acid and derivatives thereof are used as competitive inhibitors and can inhibit MARS from converting homocysteine (Hcy) into homocysteine thiolactone (HTL), so that N-homocysteine modification of protein is inhibited; the inhibitor and the acceptable derivatives thereof can also be applied to preparation of drugs for preventing or treating hyperhomocysteinemia related diseases.

The invention discloses a selenium-rich walnut protein angiotensin converting enzyme inhibitory active peptide as well as a preparation method and application thereof. The peptide SeMYHAN (682.1934 Da) provided by the invention forms 10 hydrogen bonds with 8 amino acid residues on ACE (Angiotensin Converting Enzyme), and can be used as a non-competitive inhibitor to be combined with the ACE to play a role (IC50 is equal to 0.123 mg / mL). In addition, the SeMYHAN can increase the NO release amount of EA.hy926 cells and reduce the expression amount of ET-1 in the cells, and the blood pressure lowering effect of the SeMYHAN is verified on the cellular level. In a word, the selenium-rich walnut ACE inhibitory peptide SeMYHAN is expected to serve as a good antihypertensive drug, and meanwhile, a new theoretical basis is provided for high-value utilization of natural organic selenium.

The invention relates to the technical field of biomedicine, in particular to a competitive inhibitor and application thereof, and the competitive inhibitor can be specifically combined with PGK1 and has a competitive inhibition effect on combination of PGK1 and PD-1. According to the present invention, the new mechanism of mediating PD-1 activation of the PGK1 without depending on the PD-1 extracellular ligand is found, and the competitive inhibitor can directly target the PGK1 and block the interaction between the PGK1 and the PD-1 so as to avoid the activation effect of the PGK1 on the PD-1 as much as possible. The competitive inhibitor provided by the invention has a prospect of being used as an effective solution for the problem of PD-1 monoclonal antibody drug resistance.

The invention discloses an application of a competitive inhibitor of SQLE enzyme in preparation of a medicine for treating osteosarcoma. The competitive inhibitor comprises FR194738. The invention also discloses an application of the composition in preparation of drugs for treating osteosarcoma. The composition comprises a competitive inhibitor of SQLE enzyme and a chemotherapeutic drug having a synergistic effect with the competitive inhibitor. The invention verifies that the progress of osteosarcoma can be inhibited by inhibiting the SQLE through a drug for the first time, and also verifies that the SQLE inhibitor has a synergistic effect when being combined with chemotherapeutic drugs such as methotrexate, adriamycin and cis-platinum for use, thereby providing a new target and a new treatment strategy for treating osteosarcoma.

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.

A small-molecule C1 s inhibitor compound. A competitive inhibitor of C1 s, the compound having the structure of formula A1 comprising 3 rings designated as A, B, and C, and an amidine group attached to the A-ring: pharmaceutically-acceptable salts thereof, prodrugs thereof, or analogs thereof comprising an effective substitution at the A, B, and / or C ring or amidine group. Methods of inhibiting C1 s activation and treating or preventing complement-mediated diseases or conditions.

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.

Provided herein is a method of reversing serine protease accumulation, reversing cellular damage, and / or preserving extracellular matrix in an organ of a subject, comprising the steps of selecting a subject at risk of damage to the organ and administering a therapeutically effective amount of a serine protease inhibitor. The serine protease inhibitor can be an orally administered competitive inhibitor.

The invention provides competitive inhibitors of farnesyl transferase, compositions comprising the competitive inhibitors of farnesyl transferase, and their use as antifungal agents and as agents for the prevention of the formation or growth of biofilms.

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.