73 results about "Reversible inhibition" patented technology

Masking ligands for reversibly concealing the antigen-binding site of an antibody comprise epitopes of the antibody and a cleavable linker. Methods for making masking ligands comprise joining at least two copies of the epitope of an antibody to a cleavable polypeptide linker.

The present invention relates to a method of treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour, for instance an activating mutation of the EGFR or a mutation responsible for resistance or the emergence of acquired resistance to treatment with reversible EGFR and / or HER2 inhibitors or irreversible inhibitors such as CI-1033, EKB-569, HKI-272 or HKI-357, comprising administering an effective amount of the irreversible EGFR inhibitor BIBW2992 (1) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, to a person in need of such treatment, optionally in combination with the administration of a further chemotherapeutic agent, in combination with radiotherapy, radio-immunotherapy and / or tumour resection by surgery, and to the use of a BIBW 2992 (1) for preparing a pharmaceutical composition for the treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour.

The invention relates to novel application of berberine and derivatives thereof in preparation of medicines, in particular to application of berberine and derivatives thereof in preparation of indole amine 2, 3-dioxygenase IDO inhibitor, belonging to the medicine field. According to IDO inhibition activity detection, reversible inhibition judgment, inhibitor type judgment, Ki value determination and median effective inhibition concentration IC50 determination, the results show that berberine is reversible inhibitor and inhibition constant Ki is 8muM; and jatrorrhizine hydrochloride and palmatine hydrochloride are irreversible inhibitors, and the median effective inhibition concentrations IC50 thereof are respectively 123muM and 126muM. When the berberine and the derivatives thereof disclosed in the invention are used as IDO inhibitors, the application prospect is wide and the IDO inhibitors can be used for treating serious diseases such as cancers, AIDS, Alzheimer diseases, tristimania, cataract and the like with pathological feature of IDO-mediated tryptophan metabolism.

The present invention relates to compounds of the formula I, in which R0; R1; R2; R3; R4; R5, R, Q; V, G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboemboic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and / or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and / or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and / or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

The invention provides a G12C mutant K-Ras protein irreversible inhibitor, the invention also discloses the G12C mutant K-Ras protein irreversible inhibitor and a preparation method and use thereof.

The invention belongs to the medicinal field, and concretely relates to a use of a 8-nitrotryptanthrin compound as an IDO inhibitor. The 8-nitrotryptanthrin compound is a reversible IDO inhibitor, has an inhibition constant Ki of 0.054muM, has in-vitro and cell-based median effective inhibition concentrations IC50 of 0.103muM and 1.80*10<-5>muM respectively, and has an inhibition effectiveness obviously better than a present inhibitor 1-methyltryptophan (Ki of 34muM and IC50 of 340muM). 8-nitrotryptanthrin disclosed in the invention can effectively lower the abnormally-increasing IDO activity in a tumor animal model as the IDO inhibitor, and also has tumor treatment effects comprising tumor growth delaying, tumor volume reduction and in-vitro tumor cell killing. 8-nitrotryptanthrin disclosed in the invention has a wide application prospect, and can be used for treating serious diseases having the IDO mediated tryptophan metabolism approach pathology characteristics, such as cancers, the Alzheimer disease, tristimania, cataract and the like as the IDO inhibitor.

The present invention relates to compounds of the formulae I and Ia,wherein R0; R1; R3; R4; R22, Q; V, G and M have the meanings indicated in the claims. The compounds of the formulae I and Ia are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and / or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and / or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and / or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formulae I and Ia, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

The invention provides methods and compositions for rapid and reversible inhibition of platelet aggregation in human subjects in need thereof by administering compounds of the formula:alone or in combination with a second agent which can be aspirin or a thrombolytic agent.

Described herein are compositions comprising, and methods for using, biocompatible cold slurries and methods of administering the same to provide reversible inhibition of peripheral nerves in a subject in need thereof.

The invention belongs to the medicine chemical field, and more specifically relates to a novel quinazoline compound having antineoplastic activity in a formula I and a preparation method. The compound 1 has effective protein tyrosine kinases irreversible inhibition effect and / or has good internal pharmacokinetics behavior, and is an effective protein tyrosine kinases irreversible inhibitor.

The invention modifies the U1 ribonucleoprotein (U1 snRNP) at the 5' end of its RNA so that it binds specifically to an mRNA of the gene to be inactivated, in such a way that its expression is inhibited. Gene inactivation is greater with the binding of several ribonucleoproteins to several binding sites on the 3' terminal exon of the mRNA of the gene to be in-activated, concretely at specific sites around the site of initiation of polyadenylation of said mRNA. This method is used for (i) inhibiting the expression of genes of unknown function so that they can be studied and (ii) inhibiting the expression of genes that are harmful to the cell.

The stabilization of a hydrolytic enzyme in a liquid preparation is to be improved through a component that stabilizes the hydrolytic enzyme. This is accomplished by a method for adapting a hydrolytic enzyme to a component that stabilizes the hydrolytic enzyme, comprising the following method steps: a) providing a hydrolytic enzyme (starting enzyme) and a component that stabilizes the hydrolytic enzyme and that comprises a reversible inhibitor of the hydrolytic enzyme; b) changing the amino acid sequence of the hydrolytic enzyme in at least one position, by substitution, deletion or insertion; c) determining the relative activity of the hydrolytic enzyme from step b) and the relative activity of the starting enzyme in a liquid preparation; d) selecting the hydrolytic enzyme that has a reduced relative activity by comparison with the relative activity of the starting enzyme.

The invention relates to a high-yield strain Lds.0108 for producing L-alanine by fermentation. The high-yield strain is deposited in the China Center for Type Culture Collection with an accession number of CCTCC M2013361. The strain is a mutant strain by using Lactobacillus delbrueckii subsp. Bulgaricus (GIMI.155) as an initial strain, mutagenizing cells by utilization of a low energy ion implantation method, and screening by a reversible inhibition assay method. The growth temperature range of the strain is 35-40 DEG C. The optimum growth temperature is 37 DEG C and the optimum pH value is 7.0. A slope culture medium used is an MRS culture medium. Glucose and other carbohydrates are used as substrates for the strain. The L-alanine is produced by fermentation under anaerobic conditions. Impurities are removed by ultrafiltration membrane filtration and nanofiltration membrane filtration in a purifying process, thus guaranteeing the product quality. The strain and the preparation method are suitable for large-scale industrial production.

Disclosed are novel cathepsin S, K, F, L and B reversible inhibitory compounds of the formulas (Ia) and (Ib) where R1, R2, R3, R4, R5, R6, R8, R9 and X are defined herein. The compounds are useful for treating autoimmune and other diseases. Also disclosed are processes for making such novel compounds

The invention provides an umbilical cord tissue freeze preservation and unfreezing method. According to the umbilical cord tissue freeze preservation and unfreezing method, cell aggregate freeze preservation is adopted instead of single cell freeze preservation, so that cell damage apoptosis rate is reduced, and survival rate is increased; cell adhesion molecules are added to promote bonding of cells, reduce the amount of single cells, and increase cell survival rate; ultrasonic treatment is adopted so as to ensure full penetration of a refrigeration protective solution and an unfreezing protective solution into intercellular spaces, solutions are dispersed into small liquid drops, and the permeability is improved; a cell activity inhibitor is adopted for reversible inhibition of physiological activities in cells, and improving of freeze preservation effect without influencing cell activity. The umbilical cord tissue freeze preservation and unfreezing method is capable of reducing physical and chemical damages on cells in freezing and unfreezing process, and increasing cell survival rate and unfreezing rate, so it is convenient for subsequent using.

The invention provides a method for rapidly cryopreserving and resuscitating endometrial stem cells. The method is capable of reducing the probability of cell damage and apoptosis and improving the survival rate. According to the method, cryopreservation fluid or resuscitation fluid is added into the cells to perform short-term low-frequency ultrasonic treatment, so that mutually adhesive cells can produce slight loosening and gaps on premise of not damaging the cell structure, and the fluid can be dispersed into droplets and conveniently infiltrates into the cells; cell adhesion molecules arecapable of promoting mutual adhesion of the cells, so that individual cells are further reduced, and the cell survival rate is improved; and a cell activity inhibitor is capable of performing reversible inhibition on some physiological activities in the cells, and the cryopreservation effect is improved on premise of not influencing the cell activity. According to the means, physical and chemicaldamage to the cells in the cryopreservation and resuscitation process can be reduced, so that the cell survival rate and cryopreservation and resuscitation rate of the cells are improved.

The invention belongs to the technical field of medicines and in particular relates to a fibroblast growth factor receptor (FGFR) invisible inhibitor of a formula (I) as shown in the specification, ora pharmaceutically acceptable salt, a stereisomer or a tautomer thereof. The invention further relates to a medicine preparation, a medicine composition and application of the compounds. R1, R2, a cycle A, m and warhead are defined as in the specification. The compound provided by the invention has an efficient and high-selectivity inhibition function on a fibroblast growth factor receptor, can be applied to treatment on related diseases mediated by FGFR abnormity, and particularly treatment on cancer diseases.

The invention provides a tyrosine kinase irreversible inhibitor shown in a formula I or pharmaceutically acceptable salt thereof, a preparation method for the tyrosine kinase irreversible inhibitor and applications of the tyrosine kinase irreversible inhibitor. The invention belongs to the field of pharmaceutical chemistry. The tyrosine kinase irreversible inhibitor or the pharmaceutically acceptable salt thereof is very high in activity of inhibiting growth of cancer cells, and is especially remarkable in effect of inhibiting the growth of cancer cells with high expression of an epidermal growth factor receptor (EGFR) and type-2 human epidermal growth factor receptor (HER2).

The instant invention relates to compounds of formula I, diagrammed below, wherein R3, E, D and Y are defined in the application, which are useful as reversible inhibitors of monoamine oxidase-B and / or monoamine oxidase-A, and therefore useful to treat or prevent neurological diseases or conditions in mammals, preferably humans.

A composition is provided, which comprises a serine protease; a reversible inhibitor of said serine protease; and a stabilizing agent M having the formula (I): Also provided are uses of the composition as a medicament, and other uses and methods employing its various properties.

Methods and pharmaceutical compositions are disclosed for reversibly inhibiting sperm receptor activity in animals. Nicarbazin, its derivatives and modifications which retain pharmacological activity are shown to inhibit activity of zona pellucida proteins and concomitant synthesis and / or assembly of the sperm receptor on the oocyte surface necessary for fertilization. Nicarbazin is easily administered, for example by simple addition to feed of an animal and is and non-toxic to the animals, providing a safe and efficient means for controlling populations of mammals and avian species.

The invention provides a compound with irreversible inhibitor activity of G12C mutant KRAS protein, and a racemate, a stereoisomer, a pharmaceutically acceptable salt, a polymorphic substance or a solvate of the compound. The structure of the compound is shown as a formula (I) in the specification. Also provided are methods related to the preparation and use of the compounds, a pharmaceutical composition comprising the compounds, and a method of modulating G12C mutant KRAS protein activity for the treatment of conditions such as cancer.

The invention provides a composition containing serine proteinase, a reversible inhibitor of the serine proteinase and a stabilizer M with formula I. The invention also provides an application of the composition as a medicament, other applications and a method of using various characters of the composition.

The present invention provides compositions and methods for reversibly inhibiting S-adenosyl-L-homocysteine (SAH) hydrolase. The compounds of the present invention can be used as an anti-hemorrhagic viral infection agent, an immunosuppressant, a homocysteine lowering agent, or an anti-neoplasm agent. The compositions and methods of the present invention can be used for the prevention and treatment of hemorrhagic virus infection, autoimmune diseases, autograft rejection, neoplasm, hyperhomocysteineuria, cardiovascular disease, stroke, Alzheimer's disease, multiple sclerosis or diabetes. The compound of the present invention and / or used in the present invention has the formula (I):wherein Z is selected from the group consisting of carbon and nitrogen,R1 and R2 are the same or different, and are selected from the group consisting of Hydrogen, hydroxy, alkyl, cycloalkyl, alkenyl, alkoxy, amino, aryl, heteroaryl, and halogen;R3 and R4 are the same or different and are selected from the group consisting of Hydrogen, alkyl, acetyl, alkenyl, aryl, and heteroaryl;X is selected from the group consisting of oxygen, nitrogen, and sulfur; andY is selected from the group consisting of hydrogen, a C1-10 alkyl group, alkenyl, vinyl, aryl, and heteroaryl, provided that the compound is not (4-adenine-9-yl)-2-hydroxybutanoic acid.

Methionine aminopeptidases catalyse the co-translational removal of amino terminal methionine residues from nascent polypeptide chains. A newly-discovered enzyme, designated methionine aminopeptidase type-3 (MetAP-3), has a substrate specificity which is similar to MetAP-1 and MetAP-2, although it is not inhibited by fumagillin, an irreversible inhibitor of MetAP-2. MetAP-3 also preferentially localizes to mitochondria, unlike MetAP-1 and MetAP-2, which accumulate in the cytoplasm. One embodiment of the present invention relates to human cDNAs encoding polypeptides comprising MetAP-3. Other embodiments of the invention relate to nucleic acid molecules derived from these cDNAs, including complements, homologues, and fragments thereof, and methods of using these nucleic acid molecules, to generate polypeptides and fragments thereof. Other embodiments of the invention relate to antibodies directed against polypeptides comprising MetAP-3, and methods to screen for compounds or compositions that preferentially or specifically effect the activity of polypeptides comprising MetAP-3.

The application provides a novel tyrosinase inhibitor. Golden cassia tea is used as a raw material for extracting the tyrosinase inhibitor, and a condensed tannin extract is obtained by extracting, separating and purifying by the steps of acetone extraction, centrifugation, extraction, Sephadex LH-20 column chromatography, and the like. The extract is prepared from procyanidine, a homopolymer formed by propelargonidin and prodelphinidins, and a heteropolymer, wherein the procyanidine is taken as a main component. The extract has an obvious inhibitory influence effect on the activity of tyrosinase, and has the half inhibition rate of 54.8+ / -1.27mu g / mL; the inhibition type of the extract is reversible inhibition, and the inhibition mechanism of the extract is in a hybrid type. The tyrosinase inhibitor provided by the application is convenient in material obtaining, low in price and simple and convenient to operate, thus having wide application prospect in the fields such as medical cosmetology, fruit and vegetable preservation and pest and disease control.