49 results about "Isocitrate Dehydrogenase-I" patented technology

The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula:

where A, U, W₁, W₂, W₃, R₁-R₆, and R₉ are described herein.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of IDH1 and mutant IDH1 gene expression and/or activity, and/or modulate an IDH1 or mutant IDH1 gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules, including small nucleic acid molecules such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules, that are capable of mediating or that mediate RNA interference (RNAi) against IDH1 or mutant IDH1 gene expression.

The invention discloses construction and applications of a corynebacterium glutamicum mutant strain for producing L-homoserine, and belongs to the technical field of fermentation engineering. Corynebacterium glutamicum ATCC 13032 is taken as a starting strain to knock out regulatory protein McbR, homoserine kinase, transport protein MetD, phosphoenolpyruvate carboxykinase; the expression of isocitrate dehydrogenase is down regulated; transport protein BrnFE, aspartic semialdehyde dehydrogenase and homoserine dehydrogenase are overexpressed; and the expression of aspartate kinase, pyruvate carboxylase and the aspartate kinase I derived from escherichia coli are enhanced. Shake flask culture can be performed on the mutant strain for 48 h, and the yield of L-homoserine can reach 8.8 g/L.

The invention discloses a cold-resistant gene engineering application method of rice OsICE2 gene. The method includes: (1) gene cloning, (2) vector construction, (3) transgenosis, (4) analysis of the cold-resistant phenotype of OsICE2 by a transgenic technology, and (5) comparative analysis of a transgenic plant and a control plant in the cold-resistant physiological aspect. By the steps, the method determines the influence of OsICE2 gene on protein expression quantity under low temperature stress, and finds that a transgenic rice strain can slow down the reduction of protein expression quantity of RuBi sCO subunit binding-protein alpha subunit, RuBi sCO activase small isoform precursor, Chlorophyll a-b binding protein and isocitrate dehydrogenase under low temperature stress, and improves the expression increase range of 70 kDa heat shock-related protein.

The invention discloses corynebacterium glutamicum capable of increasing lysine yield and a constructing method of the corynebacterium glutamicum, and belongs to the technical field of genetic engineering. A genetic engineering method is adopted for substituting IDH (isocitrate dehydrogenase) coding gene icdCg in corynebacterium glutamicum RG for IDH coding gene icdSm in streptococcus mutans, andaccordingly, affinity of IDH to different redox cofactors is regulated, the problem of intracellular redox imbalance in the synthesis process of L-lysine is solved, and the L-lysine accumulation capacity of the strain is improved. Tank (5L fermentation tank) experiments show that L-lysine accumulation amount of the recombinant bacterium reaches 121.4 g/L. Redox cofactor affinity of IDH in corynebacterium glutamicum is successfully changed, problem of intracellular redox imbalance during synthesis of L-lysine is solved, and a new idea for breeding the L-Lysine high-yield strain is provided.

This document relates to methods and materials involved in assessing isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutations in a mammal (e.g., human). For example, this document provides methods and materials for diagnosis, characterization, determining prognosis, and treatment of cholangiocarcinoma tumor in a mammal.

The invention provides a method for synthesizing glyoxylic acid by utilizing corynebacterium glutamicum based on CRISPRi (clustered regularly interspaced short palindromic repeats i) regulation. According to the method, an acetaldehyde dehydrogenase coding gene of the corynebacterium glutamicum is replaced through a dCas9 expression cassette gene; a lactic dehydrogenase encoding gene of corynebacterium glutamicum is replaced by sgRNA transcription units of an isocitrate dehydrogenase encoding gene and a malic acid synthetase encoding gene, an isocitrate lyase encoding gene of the corynebacterium glutamicum is over-expressed to obtain a corynebacterium glutamicum engineering strain, and the engineering strain is cultured to ferment and synthesize glyoxylic acid. Corynebacterium glutamicum is used as a starting strain, a lactic dehydrogenase coding gene and an acetaldehyde dehydrogenase coding gene which are key enzymes of branch metabolism of the corynebacterium glutamicum are knocked out, a CRISPRi regulation system is established, expression levels of an isocitrate dehydrogenase coding gene and a malic acid synthase coding gene are reduced, and meanwhile, an isocitrate lyase coding gene is overexpressed, so that a method for biosynthesizing glyoxylic acid by using corynebacterium glutamicum is established.

The invention discloses primers, a reagent kit and a method for detecting IDH1 (isocitrate dehydrogenase 1) R132H gene variation by the aid of ddPCR (droplet digital polymerase chain reaction) technologies. The method includes extracting cfDNA (cell-free deoxyribonucleic acid) in peripheral blood; designing two probes and a pair of primers for IDH1R132H mutant types and wild types; carrying out ddPCR amplification by the aid of the cfDNA used as a template; carrying out data analysis on obtained amplification products to obtain absolute quantities and proportions of IDH1R132H mutant genes. Thereagent kit for detecting the IDH1R132H gene variation is based on the method. The primers, the reagent kit and the method have the advantages that provided primer amplification fragments 83bp are particularly applicable to amplifying small-fragment DNA samples such as plasma free DNA and can be combined with the detection probes, accordingly, the IDH1R132H gene variation with extremely low abundance can be detected from the cfDNA, the primers, the reagent kit and the method are good in specificity and high in sensitivity, human IDH1R132H gene variation can be absolutely quantitatively detected by the aid of the primers, the reagent kit and the method, and important effects can be realized by the primers, the reagent kit and the method for guiding clinical treatment and improving patientprognosis; the IDH1R132H gene variation can be detected only by the aid of the peripheral blood without tissue specimen collection, and accordingly the method is particularly suitable for patients intolerant to tissue sampling.

The invention belongs to the technical field of gene engineering, and particularly relates to the construction and the application of a gene engineering bacterium for producing hydroxyectoine. According to the invention, key genes in a hydroxyectoine synthesis route are strengthened on the genome, a hydroxyectoine competitive inhibition route is weakened, the hydroxyectoine synthesis route is constructed, and an isocitrate dehydrogenase coding gene icd is over-expressed to increase the supply of a precursor alpha-ketoglutaric acid. Meanwhile, supply of a precursor substance alpha-ketoglutaric acid is dynamically adjusted and controlled through an esaI/esaR quorum sensing circuit strategy, metabolism of the alpha-ketoglutaric acid in tricarboxylic acid circulation is automatically adjusted according to the cell density, and the hydroxyectoine high-yield strain is obtained. The constructed strain can realize efficient synthesis of hydroxyectoine under the fermentation condition that alpha-ketoglutaric acid is not added, does not accumulate a byproduct ectoine, and has important industrial application value.

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

The invention relates to IDH gene dsRNA capable of improving the termite control effect of metarhizium anisopliae. The sequence design of the dsRNA is derived from a key metabolic enzyme gene, namelyan isocitrate dehydrogenase (IDH) gene, in bodies of the eupolyphaga nigromaculata and the termites nigromaculata. An IDH dsRNA template is synthesized by utilizing a specific primer of the IDH gene,and then dsIDH is generated through transcription of a T7 in-vitro transcription system. After dsIDH is introduced into a termite body by adopting an RNAi technology, the IDH gene expression is reduced, the antifungal activity of the termite is remarkably reduced, the apoptosis rate is increased, the infection level is increased, the IDH activity is reduced, the ATP level is reduced, the movementdistance is reduced, and the death rate of the termite is remarkably increased. The dsIDH can significantly improve the control effect of metarhizium anisopliae on termites, is environmentally friendly and safe to people and livestock, and has good research and application prospects.

Provided are a sultam compound having isocitrate dehydrogenase 1 (IDH1) inhibitory activity as represented by formula I or pharmaceutically-acceptable salts, solvates or hydrates thereof, a preparation method thereof, and a pharmaceutical composition containing the compound. The compound or the pharmaceutically-acceptable salts, solvates or hydrates thereof, and the pharmaceutical composition containing the compound can be used to treat IDH1 mutation-induced cancers.

It was discovered that a compound of general formula (I) that has an isoxazole skeleton has an excellent inhibitory activity on a mutated IDH1 protein, inhibits 2-HG production by the aforesaid protein and can effectively inhibit the proliferation of various tumors expressing the aforesaid protein. In general formula (I), R1, R2, R3, Y and Z are each as defined in claim 1.

The invention provides a quick detection method for IDH2 (isocitrate dehydrogenase) gene mutation, which comprises the following steps that a pair of wild type primers is designed at the two ends of an IDH2 gene mutational site; a pair of mutational type primers is designed at the mutational site; the wild type primers and the mutational type primers of an IDH2 gene are designed respectively; the primers are amplified to be a corresponding wild type template and a mutational type template respectively; the two templates are subjected to PCR (polymerase chain reaction) amplification by the wild type primers to be a corresponding wild type target fragment and a mutational type target fragment respectively; the two fragments are mixed in different proportions; and an HRM (high resolution melting) method is adopted to for distinguishing. Compared with other methods, the quick detection method has the advantages of high specificity, high sensitivity, convenience and quickness, and is higher in flux and lower in single cost.

The invention relates to a method for measuring glycine content using enzyme colorimetry and enzyme-linked method technology, the composition and components of reagents, and the technical principle of its measurement is based on the series of glycine transaminase, glutamic acid decarboxylase and isocitrate dehydrogenase After the catalytic reaction is completed, the present invention also relates to a glycine assay kit. The determination method of the invention has high sensitivity and small error, so the determination method and the kit of the invention can be widely used in food inspection.