35 results about "CYP2D6" patented technology

The present invention relates, generally to a method of determining and assessing cytochrome P450 2D6 isoenzyme (CYP2D6)-related metabolic capacity in an individual mammalian subject via a breath assay, by determining the relative amount of 13CO2 exhaled by a the subject upon intravenous or oral administration of a 13C-labeled CYP2D6 substrate compound. The present invention is useful as an in vivo phenotype assay for evaluating CYP2D6-related activity using the metabolite 13CO2 in expired breath and to determine the optimal dosage and timing of administration of CYP2D6 substrate compound.

The invention belongs to the technical field of biology, and particularly relates to an individualized medication gene testing reagent kit for a beta-receptor blocker. The individualized gene testingreagent kit for the beta-receptor blocker mainly comprises: (1) two pairs of CYP2D6*10 and ADRBB1(1165 G) [C] locus amplification and sequencing primers, (2) PCR amplification reagents, (3) a PCR product purification reagent, and (4) a DNA sequencing reagent. The reagent kit is used for detecting the loci of the beta-receptor blocker drug metabolizing enzyme and the receptor CYP2D6*10 and ADRBB1 (1165 G) [C] of the hypertension patient, uses the key technology for Sanger sequencing (the accuracy rate is more than 99.9%). The genotypes of the two loci are proved to be closely associated with the curative effect of medication of the beta-receptor blocker, so that the gene testing reagent kit can be used for guiding the hypertension patient in using the beta-receptor blocker drug reasonably and safely according to the testing result of the gene testing reagent kit.

The invention provides a primer probe combination, a kit and a method for detecting copy number variation and genotyping of human CYP2D6. The nucleotide sequences of the primer probe combination for detecting the copy number variation of the human CYP2D6 are as shown in SEQ ID No.1 to SEQ ID No.9, and the nucleotide sequences of the primer probe combination for detecting the genotyping of the human CYP2D6 are as shown in SEQ ID No.10 to SEQ ID No.17. The primer probe combination can be used for in-vitro qualitative detection of CYP2D6 copy number variation and * 10 and * 41 genotypes in human genome DNA, realizes simultaneous detection of * 10 and * 41 genotypes in a single tube on imported / domestic fluorescent quantitative PCR equipment without mutual interference, has the advantages of high accuracy, good stability and excellent detection limit, and has a wide application prospect. According to the detection result, clinical selection of antipsychotic drugs can be assisted to realize medication guidance for mental / depression patients, the curative effect is ensured, and toxic and side effects are reduced.

The invention discloses a construction method of a humanized CYP2D6*10 transgenic mouse. According to the method, the homologous recombination principle is utilized, an ES targeting mode is adopted, an expression cassette of hCYP2D6*10 is knocked into an exon4-5 site of the Cyp2d22 gene in a fixed-point mode, and then a Cyp2d gene cluster is knocked out in a Crispr / Cas9 mode; firstly, a targeting vector is prepared, and ES cells are electrically transfected after the vector is linearized; through long-fragment PCR identification, positive clones of correct homologous recombination are obtained; and the positive ES cell clone is amplified to be injected into a blastocyst of a C57BL / 6J mouse to obtain a chimeric mouse. Compared with a non-transgenic mouse, the humanized CYP2D6*10 transgenic mouse bred by the invention can express a human CYP2D6*10 type gene (dominant proportion allele of Chinese population), and can replace human beings to be used for developing pharmacokinetic and pharmacodynamic related research of substrate drugs.

The invention discloses a fluvoxamine clinical precise application virtual simulation experiment platform based on a CYP2D6 genotype, the platform is oriented to clinical problems, a complete knowledge system of laboratory research and pharmaceutical service is built, students' understanding of precise medication is cultivated, and specifically, according to the project, students are guided to understand and master gene sequencing and analysis according to the ideas of drug monitoring, drug enzyme gene detection, metabolic type judgment, guide searching and individualized drug administration scheme making of special crowds.

Compounds of Formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, metabolites thereof, derivatives thereof, prodrugs thereof, acid addition salts thereof, pharmaceutically acceptable salts thereof, or N-oxides thereof; or a combination thereof; processes and intermediates for preparation thereof, compositions thereof, and uses thereof; are provided. Pharmaceutical compositions comprising a compound of Formula I, or enantiomers thereof, metabolites thereof, derivatives thereof, prodrugs thereof, acid addition salts thereof, pharmaceutically acceptable salts thereof, or N-oxides thereof; or a combination thereof; wherein the compound is a double and / or triple agent or ligand for CYP2D6, 5-HT2A, and / or 5HT2C receptors, and / or acetylcholinesterase are provided.

Reference controls for use with pharmacogenomic testing, and methods for their identification, preparation, and use, are disclosed. The reference controls can confirm that pharmacogenomic testing correctly identifies individuals that do or do not have the mutation of interest, in both clinical trial and patient treatment settings. The reference controls can be selected to include one or more mutations to be identified, and prescreened to confirm that they bind to one or more of the primers used in the pharmacogenomic testing. The reference controls are human genomic DNA that includes certain identified polymorphisms (mutations) of interest, ideally derived from individuals, pre-selected and optionally properly consented, which have one or more of the polymorphism(s) of interest. The reference controls can be prepared by targeted pre-screening of human patients, by examining the genotype or genetic profile of the patients, isolating cells with the desired mutation, optionally immortalizing the cells, and obtaining DNA from the cells. The prescreening of prospective donors can be targeted based on any of a number of factors, such as genes of interest, mutations within the genes of interest, and membership in a specific ethnic or disease state population. The genomic DNA can be pre-screened for its ability to be detected, using a standard pharmacogenomic test, as including a specific mutation. Examples of mutations of interest include those present in a Phase I or Phase II metabolic enzyme such as CYP2D6, CYP2C19, CYP2C9, CYP2C8, and CYP3A5, CYP3A4, CYP2A6, CYP2B6, UGT1A1, DPD, ERCC1, MDR1, ADH2, NAT1 and NAT2 or any other metabolic or disease gene.

The invention discloses a gene fragment for enhancing detoxification function and a transformed HepG2 cell, wherein the gene fragment for enhancing detoxification function is composed of three gene fragments of OTC, ARG1 and OATP1B1 in sequence. In HepG2 cells transformed with this gene fragment, the expression of albumin was doubled; the expression of aspartate aminotransferase was increased by 10%; the secretion of key proteins related to endogenous detoxification ability in the cytochrome P450 family was increased, and the detoxification ability was improved: the secretion of CYP2C9 was increased by 5 times, CYP2D6 secretion increased by 50 times, CYP2A6 secretion increased by 2 times, and CYP3A4 secretion increased by 100 times.

A method of dosing LSD in treating patients, by assessing genetic characteristics in the patient by identifying polymorphisms of CYP2D6 before use of a composition chosen from the group consisting of LSD, analogs thereof, derivatives thereof, and salts thereof, administering the composition to the patient based on the patient genetics, wherein a 50% dose is administered in a patient with non-functional CYP2D6 compared to a dose in functional CYP2D6 individuals, and producing maximum positive subjective acute effects in the patient and / or reducing anxiety and negative effects. A method of determining a preferred dose of LSD.

The present invention relates to htSNPs for determining a genotype of cytochrome P450 1A2 (CYP1A2), 2A6 (CYP2A6) and 2D6 (CYP2D6), PXR and UDP- glucuronosyltransf erase Ia (UGTlA) genes and a gene chiThe present invention relates to htSNPs for determining a genotype of cytochrome P450 1A2 (CYP1A2), 2A6 (CYP2A6) and 2D6 (CYP2D6), PXR and UDP- glucuronosyltransf erase Ia (UGTlA) genes and a gene chip using the same, and more particularly, to a selection method of htSNPs for determining a haplotype of human CYP1A2, CYP2A6, CYP2D6, PXR and UGTlA genes, a method of determining a genotype of the genp using the same, and more particularly, to a selection method of htSNPs for determining a haplotype of human CYP1A2, CYP2A6, CYP2D6, PXR and UGTlA genes, a method of determining a genotype of the genes by using the htSNPs and a gene chip therefor.es by using the htSNPs and a gene chip therefor.