32 results about "Drug resistant mutants" patented technology

The present invention is directed to compounds, compositions and methods for treating or preventing viral infections, in particular, HIV, HBV, and HCV, in human patients or other animal hosts. The compounds are 3′-azido-2′,3′-dideoxy purine nucleosides or phosphonates, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1 resistance mutants including HIV-1K65R, HTV-1K70E, HIV-1L74V, HIV-1M184V, HIV-1Q151M and inhibitory activity against HIV-1 RT harboring TAMS or insertion mutations including HIV-1AZT3, HIV-1AZT7, HIV-1AZT9, HIV-1Q151M, or HIV-169insertion. In one embodiment, the compounds are 3′-azido-ddA, 3′-azido-ddG, or combinations thereof, administered with one or more additional antiviral agents that select for TAM mutations and / or the M 184V mutation, along with a pharmaceutically acceptable carrier.

The invention relates to a 2-arylaminopyridine, pyrimidine or triazine derivative and a preparation method and application thereof. The 2-arylaminopyridines, pyrimidines or triazine derivatives may act on certain mutant forms of epidermal growth factor receptors such as L858R activating mutants, delE746_A750 mutants, Exonl9 deletion activating mutants and T790M drug resistant mutants , for use in the treatment and prevention of diseases and conditions. The 2-arylaminopyridine, pyrimidine or triazine derivatives are useful for the treatment and prevention of cancer. The present invention also relates to pharmaceutical compositions comprising 2-arylaminopyridines, pyrimidines or triazine derivatives, intermediates useful in the preparation of 2-arylaminopyridines, pyrimidines or triazine derivatives, and the use of 2-arylamino Pyridine, pyrimidine or triazine derivatives in the treatment of diseases mediated by various forms of EGFR.

The invention provides novel compositions and methods for detecting unlabeled nucleic acid targets using labeled polynucleotide probes and partially complementary antiprobes. The interaction of probes, antiprobes and targets result in signaling changes that indicate target frequency. This novel detection mechanism is called a DNA detection switch, and it enable end-point detection, microarray detection and real-time PCR detection of a variety of nucleic acid targets including microbial species and subspecies, drug resistant mutants, and pathogenic strains.

Compositions and methods are provided for amplifying and or detecting nucleic acid targets using labeled polynucleotide probes and antiprobes that interact together and with complementary targets. Competitive thermodynamic interactions of these components result in signaling changes that indicate target frequency, and can provide error-checking functions that facilitate single base discrimination. These probe:antiprobe compositions enable real-time PCR detection, end-point detection and microarray detection of microbial species, drug resistant mutants, and cancer related variants. Some probe:antiprobe systems function as an internal probe, between two primers, and some function as a primer-probe. Some target sequences are discriminated or quantified by employing two probe:antiprobe systems to detect different aspects of the same template.; Systems are also provided that enhance target amplification and detection for specific single base variants. A probe may also be modified by introducing a base mismatch to increase thermodynamic discrimination of a correct versus incorrect target differing by a single base.

The invention relates to a diagnostic reagent of candida and particularly relates to a nucleic acid film strip and a kit capable of simultaneously performing identification of candida species and detection of gene mutation. The nucleic acid film strip for identification of candida species and detection of gene mutation comprises a substrate and nucleic acid probes immobilized on the substrate, wherein the nucleic acid probes comprise a nucleic acid probe used for identification of candida species and having base sequences shown in SEQ ID NO: 1-7, a nucleic acid probe used for detection of gene mutation of candida albicans and having base sequences shown in SEQ ID NO: 8-23 and an internal reference nucleic acid probe having a base sequence shown in SEQ ID NO: 24. The nucleic acid film strip and the kit are used for identification of the species and detection of drug-resistant mutant genes according to the gene sequences of candida, judging from molecular structure, results are accurate and reliable and the detection sensitivity is high; the detection time is short and the detection can be completed only just in eight hours.

The invention discloses cyclohexene compounds and an application thereof, and belongs to the field of medicinal chemistry. The cyclohexene compounds are cyclohexene compounds having a structure characteristic represented by the formula I and pharmaceutically acceptable salts and ester prodrugs or stereoisomers thereof; the cyclohexene compounds are subjected to influenza virus neuraminidase activity detection and are confirmed to have good inhibition activity on both wild type and drug-resistant mutant type influenza viruses; a part of the compounds have the inhibition activity IC50 on the wild type and drug-resistant mutant type influenza virus neuraminidase of less than 5 nM, and have the effect for significantly inhibiting the influenza viruses; the cyclohexene compounds or the pharmaceutically acceptable salts or the stereoisomers thereof are showed to have a good application prospect in preparation of anti-influenza virus drugs, thereby providing a new drug choice for clinic treatment of influenza.

The invention discloses a mycobacterium tuberculosis drug-resistant mutant gene detection kit comprising: (1) a gene chip which has (i) a nucleotide probe, wherein the probe is a sequence of SEQIDNos: 1-31 or a complementary sequence of SEQIDNos: 1-31, (ii) a DNA sequence labeled with biotin points, wherein the sequence is SEQIDNO. 32, (iii) an IS6110DNA sequence of a mycobacterium tuberculosis complex, wherein the sequence is SEQIDNo. 33; (2) various primers used for amplifying DNA sequences in clinical samples, wherein the DNA sequences of the primers are SEQIDNos. 34-41. The kit of the invention detects the drug resistance of mycobacterium tuberculosis to rifampin and isoniazid, provides reference basis for the prevention and treatment of tuberculosis, and has significant meaning.

The invention provides novel compositions and methods for detecting unlabeled nucleic acid targets using labeled polynucleotide probes and partially complementary antiprobes. The interaction of probes, antiprobes and targets result in signaling changes that indicate target frequency. This novel detection mechanism is called a DNA detection switch, and it enable end-point detection, microarray detection and real-time PCR detection of a variety of nucleic acid targets including microbial species and subspecies, drug resistant mutants, and pathogenic strains.

The invention provides a method for amplifying four genes of Botrytis cinerea and a multiplex PCR (polymerase chain reaction) primer set thereof, relating to the field of molecular biology. On the basis of drug-resistant mutant sites of known Botrytis cinerea p-benzimidazole, boscalid, iprodione, fenhexamid and many other bactericides, a PCR primer set for simultaneously amplifying four gene segments beta-tub, BsOS1, erg27 and SdhB is established. The extracted Botrytis cinerea genome can be directly used as a template and subjected to amplification by using the designed primer set to obtain the enriched four gene segments. The multiplex PCR process is used for the first time to simultaneously amplify the four drug-resistant mutant genes of Botrytis cinerea, thereby greatly reducing the workload for drug-resistant site detection in the later period. By optimizing the PCR reaction system, the four gene segments are amplified in one PCR process.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a 4,6-pyrimidine diamine compound and a preparing method and an application thereof; the 4,6-pyrimidine diamine compound is an N4,N6-(2,5-dialkoxy phenyl)-pyrimidine diamine compound or an N4-(2,5-dialkoxy phenyl)-N6-(3-alkoxy phenyl)-pyrimidine diamine compound, and in particular, alkoxy can be C1-C4 alkane. The 4,6-pyrimidine diamine compound can be used for broad-spectrum inhibition of the activity of an EGFR kinase and resisting of EGFR expressed tumor cell activity. The EGFR kinase is a wild-type or drug-resistant mutant EGFR kinase, and provides a basis for new drug screening. And the synthesis method of the 4,6-pyrimidine diamine compound provided by the invention is simple in synthesis process and is in favor of industrialized production.

Probe systems and methods are provided for detecting nucleic acid targets using labeled polynucleotide probes and antiprobes that interact together and with complementary targets. These interactions result in signaling changes that indicate target frequency and provide error-checking functions that facilitate single base discrimination. These probe:antiprobe compositions enable real-time PCR detection, end-point detection and microarray detection of microbial species, drug resistant mutants, and cancer related variants. The probe:antiprobe may be an internal probe between two primers or may be a primer-probe. The probe also may be modified by introducing a base mismatch to increase thermodynamic discrimination of a correct versus incorrect target differing by a single base. Probe systems also are provided for use in methods of increasing target amplification and detecting specific single base variants.

The invention discloses an amplification primer for detecting a drug-resistant mutant gene of HCV (hepatitis c virus) 2a subtype NS5A, application and a detection method. The amplification primer fordetecting a drug-resistant mutant gene of HCV 2a subtype NS5A comprises a first amplification primer pair, wherein sequences of an upstream primer and a downstream primer in the first amplification primer pair are shown by SEQ ID NO:1 and SEQ ID NO:2 respectively. The amplification primer for detecting a drug-resistant mutant gene of HCV 2a subtype NS5A can be used for analyzing and studying the mutation condition of the HCV gene so as to provide reference for clinical study on drug resistance. When the amplification primer is adopted to perform detection and analysis such as PCR amplification, the effectiveness is high, the detection success rate can reach 100%, the reproducibility is high, and particularly, the minimum detection limit is low, thus the detection of a sample with low HCV RNA concentration is facilitated while the sensitivity is high.

The invention relates to the field of pharmaceutical chemistry, in particular to benzoic acid triazole anti-influenza-virus compounds as well as a preparation method and a pharmaceutical application thereof. A pharmacological testing result shows that the compounds have an efficient inhibition effect on influenza viruses and oseltamivir drug-resistant mutants in vitro and vivo. Therefore, the compounds can be used for treating influenza.

The invention discloses a method for increasing yield of toyocamycin through screening of united drug-resistant mutant strains and belongs to the field of microbial technologies. According to the method, Streptomyces diastatochromogenes D mutant strains generating drug resistance to low-concentration streptomycin, high-concentration streptomycin and paromomycin are obtained through screening of the united drug-resistant mutant strains, and the toyocamycin productivity of the obtained mutant strains is remarkably improved when compared with that of Streptomyces diastatochromogenes D.

The invention relates to a mycobacterium tuberculosis pyrazinamide molecule drug sensitivity detection method, which aims at solving the problems to find a drug sensitivity target of mycobacterium pyrazinamide, to provide a pyrazinamide drug-resistant mutant library due to a pyrazinamide drug sensitivity target mutation on the basis, and to perform fast drug sensitivity detection by a molecule drug sensitivity detection technology. The detection method provided by the invention is simple and effective; clinic users can use the pyrazinamide molecule drug sensitivity result judgment to monitor the drug sensitivity of clinic tuberculosis patients according to an experiment method; the drug use is guided; the generation of pyrazinamide-resistant strains is reduced; and a novel and effective method is provided for clinic application and scientific study.

The present invention discloses an HIV-1B subtype drug-resistant mutant and a construction method and application thereof. In accordance with the method provided by the present invention, the reverse transcriptase of an HIV-1B subtype wild strain is mutated from threonine to valine from the 369th amino acid residue at the N tail end, so as to obtain an HIV-1B subtype drug-resistant mutant. The present invention is significant for the sifting of HIV-resistant drugs, thereby having far-reaching influence on the cure of AIDS.

The invention belongs to the technical field of biological medicine, relates to a drug for clinical treatment of HBV infection diseases, and provides application of the natural active material baicalin capable of specifically inhibiting the host nuclear transcription factor HNF (hepatocyte nuclear factor) to preparation of anti-HBV drugs, and application of a pharmaceutical composition composed of a baicalin compound and a nucleoside compound to preparation of drugs for clinical treatment of HBV infection diseases. Experiments prove that baicalin inhibits the replication activity of HBV by interfering with the nuclear transcription factor, and has a remarkable wild type and lamivudine-resistant mutant strain HBV replication inhibiting effect; after being combined with nucleoside analogs, baicalin can effectively improve the HBV drug-resistant mutant strain intervening effect and reduce the toxic and side effects of nucleoside drugs, and can be used for preparing drugs for clinical treatment of HBV infection diseases.

The invention discloses a strain kit for screening and evaluating AIDS (acquired immune deficiency syndrome) therapeutic drugs. The invention provides a kit which comprises 7 recombinant HIVs (human immunodeficiency viruses): HIV-M46I virus strain, HIV-I54V virus strain, HIV-V82A virus strain, HIV-M46I / N88S virus strain, HIV-G48V / I54V virus strain, HIV-M46I / V82T / I84V virus strain and HIV-G48V / I54V / V82A virus strain. Site-directed mutagenesis is utilized to establish a set of HIV-1 proteinase inhibitor drug-resistant mutant strains. The earlier stage test proves that the HIV-1 proteinase inhibitor drug-resistant mutant strains have certain drug resistance to the proteinase inhibitors in the market at present. The new drugs can only have potential marketing value when having favorable antivirus effects for the strains. Therefore, the kit is applicable to preclinical pharmacodynamic evaluation of AIDS therapeutic drugs.

The invention discloses a combination of primers and probes for detection of carbendazim-resistant strains of Fusarium graminearum and a detection method thereof. The primer-probe combination consists of forward primer tub2F, reverse primer tub2R, three drug-resistant mutants and wild-type probes 167m, 198m, 200m, 167w, 198w, and 200w. The detection method of the present invention can simultaneously detect three different types of drug-resistant mutations, and has high throughput, strong specificity and scalability, high signal-to-noise ratio, high sensitivity, high degree of automation, strong practicability, and can meet the requirements of anti-carbendazim and The rapid detection of Fusarium valley provides a basis for scientific and rational drug use.

The invention discloses a PCR-CRISPR detection method for targeting a HBV drug-resistant mutant gene. The method comprises the following steps: (1) performing PCR amplification on nucleic acid of a sample to-be-tested with a pair of specific primers, wherein a 5' end of an upstream primer is provided with a sequence recognizable and transcribed by T7 RNA polymerase; and (2) detecting whether the drug-resistant mutant gene is in an amplification product of the sample nucleic acid to-be-detected in a detection system including crRNA, T7 RNA polymerase, Cas13a protein, and an RNase reporter molecule that recognizes a HBV YMDD-resistant mutation site, and a target sequence of the drug-resistant mutant gene is a YIDD or YVDD gene mutation of a YMDD region of a HBV genome. The present inventionalso discloses crRNA capable of targeting a YIDD or YVDD resistance gene mutation of HBV and a kit containing the same. The method provided by the invention can detect HBV drug-resistant mutant gene simply and quickly, and has extremely high sensitivity and specificity.

The invention discloses a mycobacterium tuberculosis drug-resistant mutant gene detection kit comprising: (1) a gene chip which has (i) a nucleotide probe, wherein the probe is a sequence of SEQIDNos: 1-31 or a complementary sequence of SEQIDNos: 1-31, (ii) a DNA sequence labeled with biotin points, wherein the sequence is SEQIDNO. 32, (iii) an IS6110DNA sequence of a mycobacterium tuberculosis complex, wherein the sequence is SEQIDNo. 33; (2) various primers used for amplifying DNA sequences in clinical samples, wherein the DNA sequences of the primers are SEQIDNos. 34-41. The kit of the invention detects the drug resistance of mycobacterium tuberculosis to rifampin and isoniazid, provides reference basis for the prevention and treatment of tuberculosis, and has significant meaning.

The invention provides a method for amplifying four genes of Botrytis cinerea and a multiplex PCR (polymerase chain reaction) primer set thereof, relating to the field of molecular biology. On the basis of drug-resistant mutant sites of known Botrytis cinerea p-benzimidazole, boscalid, iprodione, fenhexamid and many other bactericides, a PCR primer set for simultaneously amplifying four gene segments beta-tub, BsOS1, erg27 and SdhB is established. The extracted Botrytis cinerea genome can be directly used as a template and subjected to amplification by using the designed primer set to obtain the enriched four gene segments. The multiplex PCR process is used for the first time to simultaneously amplify the four drug-resistant mutant genes of Botrytis cinerea, thereby greatly reducing the workload for drug-resistant site detection in the later period. By optimizing the PCR reaction system, the four gene segments are amplified in one PCR process.

The invention belongs to the field of medicine preparation and particularly relates to application of a bis-indole compound FGFC1 in preparation of medicaments resistant to non-small cell lung cancer.The medicaments resistant to non-small cell lung cancer are EGFR-targeted medicaments resistant to human non-small cell lung cancer. EGFR sensitive and drug-resistant mutant cell lines are PC9 and H1975. The medicaments resistant to non-small cell lung cancer are at least made in one preparation form of tablets, capsules, granules, drop pills, suspensions, syrups, enteric preparations, emulsion suspensions and injections. The bis-indole compound FGFC1 not only has the potential of being developed into a new generation of the EGFR-targeted medicaments resistant to non-small-cell lung cancer but also has a potential application value in the fields of targeting medicaments, probe design and fluorescent biomarkers of non-small-cell lung cancer.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a 4,6-pyrimidine diamine compound and a preparing method and an application thereof; the 4,6-pyrimidine diamine compound is an N4,N6-(2,5-dialkoxy phenyl)-pyrimidine diamine compound or an N4-(2,5-dialkoxy phenyl)-N6-(3-alkoxy phenyl)-pyrimidine diamine compound, and in particular, alkoxy can be C1-C4 alkane. The 4,6-pyrimidine diamine compound can be used for broad-spectrum inhibition of the activity of an EGFR kinase and resisting of EGFR expressed tumor cell activity. The EGFR kinase is a wild-type or drug-resistant mutant EGFR kinase, and provides a basis for new drug screening. And the synthesis method of the 4,6-pyrimidine diamine compound provided by the invention is simple in synthesis process and is in favor of industrialized production.

The invention belongs to the field of medicine preparation, and particularly relates to the application of bisindole compound FGFC1 in the preparation of anti-non-small cell lung cancer drugs. The anti-non-small cell lung cancer drug is an anti-human non-small cell lung cancer drug targeting EGFR. The EGFR sensitive and drug-resistant mutant cell lines are PC9 and H1975. The anti-non-small cell lung cancer drug is at least one of tablet, capsule, granule, drop pill, suspension, syrup, enteric-coated preparation, emulsion suspension and injection. The bisindole compound FGFC1 of the present invention not only has the potential to be developed into a new generation of anti-non-small cell lung cancer drugs targeting EGFR, but also has potential in the fields of targeted drugs, probe design and fluorescent biomarkers for non-small cell lung cancer. Value.

The invention relates to a reagent for diagnosing drug resistance of mycobacterium tuberculosis, in particular to a membrane strip and a kit for detecting drug resistant mutant genes of the mycobacterium tuberculosis. The membrane strip for detecting the drug resistant mutant genes of the mycobacterium tuberculosis fixes a specific oligonucleotide probe which is used for detecting the drug resistant mutant genes of the mycobacterium tuberculosis on a substrate. The kit for detecting the drug resistant mutant genes of the mycobacterium tuberculosis comprises the membrane strip which is fixed with the specific oligonucleotide probe used for detecting the drug resistant mutant genes of the mycobacterium tuberculosis and a primer of drug resistant relevant genes of specific amplification mycobacterium tuberculosis. The kit for detecting the drug resistant mutant genes of the mycobacterium tuberculosis can simultaneously detect various usual drug resistant mutant gene types on five genes such as rpoB, katG, inhA, embB and rpsL, is suitable for the diagnosis of tubercle bacilli to the drug resistance of tuberculosis resistant drugs such as rifampicin, retozide, ethambutol, streptomycin,and the like, and has the advantages of quick and accurate detection, large flux, and the like.

The invention relates to a diagnostic reagent of candida and particularly relates to a nucleic acid film strip and a kit capable of simultaneously performing identification of candida species and detection of gene mutation. The nucleic acid film strip for identification of candida species and detection of gene mutation comprises a substrate and nucleic acid probes immobilized on the substrate, wherein the nucleic acid probes comprise a nucleic acid probe used for identification of candida species and having base sequences shown in SEQ ID NO: 1-7, a nucleic acid probe used for detection of gene mutation of candida albicans and having base sequences shown in SEQ ID NO: 8-23 and an internal reference nucleic acid probe having a base sequence shown in SEQ ID NO: 24. The nucleic acid film strip and the kit are used for identification of the species and detection of drug-resistant mutant genes according to the gene sequences of candida, judging from molecular structure, results are accurate and reliable and the detection sensitivity is high; the detection time is short and the detection can be completed only just in eight hours.

The invention discloses molecular markers for detecting a carbostyril-resistant gene of bovine-derived Escherichia coli and application thereof. The molecular markers have sequences of P1, SEQ ID NO. 1 to 2, P2, SEQ ID NO. 3 to 4 and P3, SEQ ID NO. 5 to 6. The molecular markers can detect production of a drug-resistant mutant strain in real time in bacterial infection treatment, can evaluate antibiotic potencies and a drug-resistant mutation prevention capability of the antibacterial agent and have the advantages of high specificity, high sensitivity and good stability.

The invention discloses an amplification primer for detecting a drug-resistant mutant gene of HCV (hepatitis c virus) 2a subtype NS5A, application and a detection method. The amplification primer fordetecting a drug-resistant mutant gene of HCV 2a subtype NS5A comprises a first amplification primer pair, wherein sequences of an upstream primer and a downstream primer in the first amplification primer pair are shown by SEQ ID NO:1 and SEQ ID NO:2 respectively. The amplification primer for detecting a drug-resistant mutant gene of HCV 2a subtype NS5A can be used for analyzing and studying the mutation condition of the HCV gene so as to provide reference for clinical study on drug resistance. When the amplification primer is adopted to perform detection and analysis such as PCR amplification, the effectiveness is high, the detection success rate can reach 100%, the reproducibility is high, and particularly, the minimum detection limit is low, thus the detection of a sample with low HCV RNA concentration is facilitated while the sensitivity is high.