130 results about "Cytochrome p450 enzyme" patented technology

The present invention features Nicotiana nucleic acid sequences such as sequences encoding constitutive, or ethylene or senescence induced polypeptides, in particular cytochrome p450 enzymes, in Nicotiana plants and methods for using these nucleic acid sequences and plants to alter desirable traits, for example by using breeding protocols.

This disclosure provides a newly developed strategy and particular options for differentiating pluripotent stem cells into cells of the hepatocyte lineage. Many of the protocols are based on a strategy in which the cells are first differentiated into early germ layer cells, then into hepatocyte precursors, and then into mature cells. The cells obtained have morphological features and phenotypic markers characteristic of human adult hepatocytes. They also show evidence of cytochrome p450 enzyme activity, validating their utility for commercial applications such as drug screening, or use in the manufacture of medicaments and medical devices for clinical therapy.

A vaginal or buccal delivery of therapeutic agents having a substrate affinity for metabolic cytochrome P-450 enzymes and membrane efflux transporter systems. A method for augmentation of systemic exposure to the therapeutic agents having a substrate affinity for cytochrome P-450 enzymes and membrane efflux transporter systems, by delivering said agents to the systemic circulation through vaginal or buccal mucosa.

Nucleic acids encoding cytochrome P450 variants are provided. The cytochrome P450 variants of have a higher alkane-oxidation capability, alkene-oxidation capability, and/or a higher organic-solvent resistance than the corresponding wild-type or parent cytochrome P450 enzyme. A preferred wild-type cytochrome P450 is cytochrome P450 BM-3. Preferred cytochrome P450 variants include those having an improved capability to hydroxylate alkanes and epoxidate alkenes comprising less than 8 carbons, and have amino acid substitutions corresponding to V78A, H236Q, and E252G of cytochrome P450 BM-3. Preferred cytochrome P450 variants also include those having an improved hydroxylation activity in solutions comprising co-solvents such as DMSO and THF, and have amino acid substitutions corresponding to T235A, R471A, E494K, and S1024E of cytochrome P450 BM-3.

The present invention provides a set of oligonucleotide probe for detecting CYP450 enzyme gene hot mutant site and its uses, belonging to clinical molecular diagnosis field. The probe is designed at whole gene sequence of each subtype enzyme of CYP450 and has relative high sensitivity and specifity. The present invention also provides a gene chip for detecting cytochrome P450 enzyme series mutant sites and can detect gene typing of DNA specimen. The inventive probe can be used in P450 genetype diagnosi, clinical medicament and preventing drug adverse reaction.

The invention discloses preparation and application of an insoluble drug-entrapped poloxamer/amphiphilic polysaccharide mixed micelle. The insoluble drug-entrapped poloxamer/amphiphilic polysaccharide mixed micelle is prepared through a dialysis method or a solvent evaporation method. The mixed micelle is low in critical micelle concentration, is high in drug-loading rate, is capable of obviously prolonging the stabilization time and has the long-circulation function of a nanomicelle and has dual functions of restraining the metabolism of P-glycoprotein and cytochrome P450 enzyme and is capable of increasing the bioavailability of oral administration. The mixed micelle is simple in preparation method, is mature in process and is high in yield and can be prepared into preparations for the oral administration, such as tablets, capsules, pills and syrups.

Disclosed is a method for detecting CYP450 enzymatic activity by means of micro-liver tissue incubation in vitro, which is characterized in that: a liver trace puncturing method used in clinic takes micro-liver tissues of 0.1 to 0.2g, or kills a mouse to take out the liver in an animal experiment, and builds a micro-liver tissue in vitro incubation system, then uses a one-probe medicine to perform the liquid phase chromatography tandem mass spectrometry for detecting probe substrates and concentration of corresponding metabolites, and obtains the activity of P450 enzyme according to metabolite ratios thereof. The method has the advantages of: 1. micro scale: only micro-liver tissues of 0.1 to 0.2g are needed for detecting cytochrome P450enzyme activity, and can be used for animal experiment and checking clinic micro-liver tissue liver drug enzyme activity; 2. time saving and convenience: costly ultracentrifugation equipment used in the conventional method is saved, costs and time for detection are greatly saved, and liver enzyme metabolic condition simulation is better; and 3. establishing indexes for evaluating the enzyme metabolic activity: metabolite ratios.

The invention relates to a specific probe substrate composition of cytochrome P450 (CYP450) enzyme and an application of the specific probe substrate composition in subtype enzyme activity detection of the cytochrome P450 enzyme. The composition comprises at least two of phenacetin, coumarin, amfebutamone, dextromethorphan, diclofenac and testosterone. The characteristics of multi-ion channels can be simultaneously detected by the specific probe substrate composition and a liquid chromatography-mass spectrometry technology, and the inhibition conditions of six CYP450 enzymes are determined simultaneously, so that the experiment flux efficiency is greatly improved, and the experiment cost is reduced.

The present invention provides nucleic acids comprising nucleotide sequences encoding modified cytochrome P450 enzymes; as well as recombinant vectors and host cells comprising the nucleic acids. The present invention further provides methods of producing a functionalized compound in a host cell genetically modified with a nucleic acid comprising nucleotide sequences encoding a modified cytochrome P450 enzyme.

The present invention provides methods and compositions for balancing electron reduction potentials of formulations in a manner that reduces susceptibility to changes from xenobiotics. The present invention also provides novel compositions of matter based on structuring from a mobile nucleotide integral to its architecture.

The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C₁-C₂₀ alkyl, unsaturated C₁-C₂₀ alkenyl, unsaturated C₁-C₂₀ alkynyl, substituted saturated C₁-C₂₀ alkyl, substituted unsaturated C₁-C₂₀ alkenyl, substituted unsaturated C₁-C₂₀ alkynyl, C₁-C₂₀ cycloalkyl, C₁-C₂₀ cycloalkenyl, substituted saturated C₁-C₂₀ cycloalkyl, substituted unsaturated C₁-C₂₀ cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (—OCR²H)_p—, wherein for each p, all R² are separately selected from the group consisting of a hydrogen atom, saturated C₁-C₂₀ alkyl, unsaturated C₁-C₂₀ alkenyl, unsaturated C₁-C₂₀ alkynyl, substituted saturated C₁-C₂₀ alkyl, substituted unsaturated C₁-C₂₀ alkenyl, substituted unsaturated C₁-C₂₀ alkynyl, C₁-C₂₀ cycloalkyl, C₁-C₂₀ cycloalkenyl, substituted saturated C₁-C₂₀ cycloalkyl, substituted unsaturated C₁-C₂₀ cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R² is hydrogen, and Q is the ether form of a phenoxide fluorophore.

The present invention provides nucleic acids comprising nucleotide sequences encoding modified cytochrome P450 enzymes; as well as recombinant vectors and host cells comprising the nucleic acids. The present invention further provides methods of producing a functionalized compound in a host cell genetically modified with a nucleic acid comprising nucleotide sequences encoding a modified cytochrome P450 enzyme.

The present invention relates to pharmaceutical compositions and to methods for their use in decreasing cytochrome P450 (CYP450) enzyme activity. The present invention also relates to methods of increasing the bioavailability of a compound in a mammal. Additionally, the present invention relates to methods of decreasing the metabolism of certain compounds in a mammal that are metabolized by the cytochrome P450 enzyme. Furthermore, the present invention relates to pharmaceutical compositions comprising at least one compound metabolized by at least one cytochrome P450 enzyme and a cytochrome P450 enzyme-inhibiting amount of a compound of formula (I).

The invention discloses a fulvestrant phosphate derivative and a preparation method and application thereof, and aims to solve the problem in the prior that the fulvestrant drug substance is poor in ordinary temperature stability. The fulvestrant phosphate derivative can be used for preparing medicines capable of preventing and treating breast cancers, and is a compound with a novel structure and fulvestrant mother ring 3-phenolic hydroxyl is carried out phosphate. According to a method for fulvestrant phosphate phosphate, the material is easy to obtain, the synthesis method is simple, and the purification manner is simple, convenient and fast. Moreover, the derivative provided by the invention is higher in stability compared with an original drug; under the catalysis of the cytochrome P 450 enzyme CYP3A4 and alkaline phosphatase, the original drug can be released, so that the kind of compound has a broad application prospect in preparing the medicines capable of preventing and treating breast cancers. The derivative has the structural formula as shown in the description.

Systems and method are provided for modeling substrate molecules so that the various pathway reaction rates, and thus their overall reaction rates and metabolic properties, can be predicted. The current invention provides various systems and methods for stoichiometrically measuring the pathway reaction rates, both directly and indirectly. By repeating this for a class or several classes of substrate molecules, a general model of pathway reaction rates can be developed by correlating observed pathway reaction rates to the actual structural descriptors of the molecules, in particular, features around the reactive sites. The model can then be used to predict and design substrates according to desired metabolic characteristics. The systems and methods are particularly applicable to metabolism of substrate molecules by the cytochrome P450 enzymes.

The invention discloses a method for heterologous biosynthesis of ganoderic acid through synthetic biological means. The method comprises the following steps: exploring cytochrome P450 enzyme (CYP) gene related to bio-synthesis of ganoderma triterpenes, and promoting heterologous expression of the gene in saccharomyces cerevisiae cells so as to achieve screening and identifying; and separating andpurifying a fermentation product of a yeast engineering strain, and conducting such analysis as mass spectrum, nuclear magnetic resonance and the like, so as to confirm 3-hydroxy-lanosta-8 and 24-dien-26-oci-acid (ganoderic acid Z). The method provided by the invention comprises a series of design and verification of exploring the bio-synthesis catalysis element (the gene) from the ganoderma triterpenes, fermentation phenotype priliminary screening and element function identifying, and finally, obtaining ganoderma triterpene substances of heterologous biosynthesis and the like, and the methodalso offers an example for heterologous production of other ganoderma triterpene active substances.

Derivatives of dillapiol, sesamol and related monolignans having the following general formula:

These compounds have synergistic properties, inhibit cytochrome P450 enzymes such as human CYP3A4, and can be used as pesticide synergists or pharmaco-enhancers. Accordingly, methods for increasing the efficacy and/or bioavailability of a pharmaceutically active agent and for increasing the potency of a pesticide are described, as are synergistic pesticidal and pharmaceutical compositions.

The invention discloses a primer group and a kit for detecting genetic typing of CYP3A5. The primer group for detecting CYP3A5 gene typing comprises a CY3A5*1 primer pair, a CY3A5*2 primer pair, a CY3A5*3 primer pair, a CY3A5*4 primer pair, a CY3A5*5 primer pair, a CY3A5*6 primer pair and an internal reference primer pair. The application of the kit helps to realize good typing for CYP3A5 gene; and in clinical application of organ transplantation, good guidance effects on individualized use and secure use of immunosuppressant are realized.