37 results about "Cyp3A4 Inducer" patented technology

The present invention is directed to a method of inhibiting CYP3A4 induction. The method involves administering a compound of the following formula:R1—X—(CH2)n—N═C═Swith R1, X, and n defined herein, binds to a Pregnane X Receptor or Steroid and Xenobiotic Receptor (SXR or NR1I2) under conditions effective to inhibit CYP3A4 gene induction. The present invention also include a method of administering a compound, described herein, together with the CYP3A4 inducer to prevent a loss of efficacy in the subject to whom the CYP3A4 inducer is repeatedly administered. In addition, such compounds can be administered to block the interaction between a CYP3A4 inducer and another drug being administered that is a substrate of CYP3A4.

The present disclosure provides for methods of treating a patient with a CYP3A4 substrate drug contraindicated for concomitant administration with a strong CYP3A4 inhibitor, wherein the patient is treated with multiple doses of posaconazole, stops posaconazole treatment, and then is treated with the CYP3A4 substrate drug. In some embodiments, treatment with the CYP3A4 substrate drug is delayed for about 2-21 after stopping posaconazole. In some embodiments, the patient is treated with or prescribed a reduced dose of the CYP3A4 substrate drug for about 2-21 after stopping posaconazole.

The invention discloses a DNA micro-array chip and a detection method thereof and the application on detecting the polymorphism of CYP3A4, CYP3A5 and MDR1 genes. The chip comprises a solid phase carrier and a probe. The nucleotide sequence of the probe is shown as SEQ ID No: 1-SEQ ID No: 49. The probe is firstly arranged on the solid phase carrier. And then the target nucleotide sequence of a sample to be detected is marked and prepared. After that, the target nucleotide sequence is hybridized with the probe on the chip. Finally, the hybridization result is detected to obtain the information of the CYP3A4, CYP3A5 and MDR1 genes in the sample to be detected. The chip of the invention can be used for the detection of a plurality of genes of a plurality of samples simultaneously once only and has the advantages of simple operation and high result accuracy. Large amount of genetic information of patients can be obtained through detection once. The DNA micro-array chip and the detection method thereof can be used for instructing the formulation of reasonable drug schemes and realizing the personalized medical treatment.

The invention belongs to the field of biological medicine, and particularly relates to a method for improving a detoxification function of hepatocyte-like cells derived from human stem cells and application of the method. The method is characterized in that the stem cells are transfected with miR-142-3p inhibitors during stem cell hepatic differentiation, and the nucleotide sequence of the miR-142-3p inhibitors is shown as SEQ ID No.1. After differentiation of the stem cells, the miR-142-3p inhibitors are transfected, after transfection, differentiation is performed and molecular and functional testing of the hepatocyte-like cells is detected, it is found that on the 8th day of stem cell hepatic differentiation, 10nM of the miR-142-3p inhibitors are transfected, and enzyme activity of CYP2E1 and CYP3A4 is the highest. The method overcomes the disadvantage of low detoxification ability of the hepatocyte-like cells derived from the human stem cells, facilitates the development of an artificial liver and the in-depth study of medical research and development by using the hepatocyte-like cells derived from the human stem cells or the artificial liver.

The invention discloses a kit for detecting the curative effect of an individual antilipemic and antiatherosclerotic drug. The kit comprises a specific primer pair, a specific fluorescent probe pair, a fluorescence quantitative PCR conventional assembly and the like, and the specific primer pair is used for detecting a medication target site, namely a CYP3A4 gene, CYP2D6 gene and CYP2C9 gene polymorphism site of the statin drug. The kit can be used for estimating the curative effect of the individual antilipemic and antiatherosclerotic drug by detecting the medication target site, namely CYP3A4 gene, CYP2D6 gene and CYP2C9 gene polymorphism siteCYP3A4 gene, CYP2D6 gene and CYP2C9 gene polymorphism site of the statin drug.

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.

A rapid and sensitive radiometric assay for assessing the activity of cytochrome P450 (CYP) 3A4 / 5 and the potential of an analyte to inhibit CYP3A4 / 5 activity or induce CYP3A4 / 5 expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.

The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to alterations in drug and chemical metabolism by modification of its structure or mechanism. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug metabolism gene such as the Cyp7b1 gene, the Cyp3a4 gene, etc. In another embodiment, the rat cell is a somatic cell. The inactivation of at least one drug metabolism allele results in an animal with a higher susceptibility to altered drug and chemical metabolism. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for altered drug and chemical metabolism or toxicology and as a test animal for autoimmune and other studies. The invention additionally pertains to the use of such rats or rat cells, and their progeny in research and medicine. In one embodiment, the invention provides a genetically modified or chimeric rat cell whose genome comprises two chromosomal alleles of a drug metabolism gene wherein at least one of the two alleles contains a mutation, or the progeny of the cell.

Described are general means and methods of diagnosing and treating the phenotypic spectrum as well as the overlapping clinical characteristics with several forms of inherited abnormal expression and / or function of the CYP3A4 and CYP3A7 genes. In particular, polynucleotides of molecular variant CYP3A4 and CYP3A7 genes which, for example, are associated with insufficient metabolization and / or sensitivity of drugs, and vectors comprising such polynucleotides are provided. Furthermore, host cells comprising such polynucleotides or vectors and their use for the production of variant CYP3A4 and CYP3A7 proteins are described. In addition, variant CYP3A4 and CYP3A7 proteins and antibodies specifically recognizing such proteins as well as transgenic non-human animals comprising the above-described polynucleotide or vectors are provided. Described are also methods for identifying and obtaining inhibitors for therapy of disorders related to the malfunction of the CYP3A4 and CYP3A7 genes as well as methods of diagnosing the status of such disorders. Pharmaceutical and diagnostic compositions comprising the above-described polynucleotides, vectors, proteins, antibodies and inhibitors by the above-described method are provided. Said compositions are particularly useful for diagnosing and treating various diseases with drugs that are substrates, inhibitors or modulators of the CYP3A4 or CYP3A7 gene product.

The invention provides a specificity probe substrate Tenuifoliside A of cytochrome P450-3A4 enzyme and application thereof in CYP3A4 enzyme activity measurement. The enzyme activity measurement includes the following operation processes: (1) with the Tenuifoliside A as the high-specificity probe substrate, carrying out a CYP catalytic reaction of a specificity substrate by means of a CYP in-vitro incubation system; and (2) quantitatively detecting the product generation amount or substrate consumption amount in unit time for determining the activity of the CYP3A4 enzyme in various bio-samples and cells. The specificity probe substrate can be used for quantitative evaluation of the CYP3A4 enzyme activity in the bio-samples from different individual sources, and quantitative measurement of the CYP3A4 single-enzyme activity of cell culture fluids and cell prepared products from different animal tissue cell sources.

The invention discloses a CYP3A4 gene SNP detection specific primer, a liquid-phase chip and a method; and the liquid-phase chip comprises wild-type and mutant ASPE primers which are respectively designed for each type of mutation points, microspheres which are respectively coated with specific anti-tag sequences, and the primer which is used for amplifying a CYP3A4 gene target sequence with CYP3A4*1B, CYP3A4*2, CYP3A4*3, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*15, CYP3A4*17, CYP3A4*18 and / or CYP3A4*19SNP sites. The CYP3A4 gene SNP detection liquid-phase chip has very good signal-noise ratio, and a designed probe and the anti-tag sequences essentially have no cross reaction. The designed ASPE primers have very good specificity and can accurately distinguish all types of mutation points. The detection method has simple steps and ten types of SNP sites can be detected at one step, so that the operation is convenient, thereby preventing a plurality of uncertain factors in a plurality of operation processes, and greatly improving the detection accuracy rate.

The invention relates to the generation of non-human transgenic animals comprising a reporter construct for producing a detectable amount of a reporter molecule operably linked to a transcriptional regulatory nucleic acid molecule from the human CYP3A4 gene located between the initiation of transcription site of the gene and a position located 13,000 nucleotides upstream from the site. The invention also relates to the use of these animals for determining the effect of a compound, particularly, but not exclusively, a xenobiotic or steroid, on the regulation of expression of the CYP3A4 gene in a human.

The invention discloses a preparing method to produce CYP3A4 polypeptide with amino acid sequence: SQNSKETESHKALSD and antihuman CYP3A4 polypeptide antibody, which comprises the following steps: (1)analysis of CYP3A4 antigen epitope; (2) synthesis of CYP3A4 polypeptide; (3)crosslinking of CYP3A4 polypeptide and carrier protein; (4) preparing antirabbit CYP3A4 polypeptide antibody; (5) assembling, separating to get serum with antibody; purifying antibody; getting antihuman CYP3A4 polypeptide antibody.