74 results about "Isocitrate dehydrogenase" patented technology

The present invention discloses uses for the IDH gene and / or polypeptide and / or modulators thereof in the diagnosis and treatment of apoptosis-related diseases.

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, B, W1, W2, W3, and R1-R8 are described herein.

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 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, B, U, V, Z, W1, W2, W3, and R1-R6 are described herein.

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, B, U, V, Z, W1, W2, W3, and R1-R6 are described herein.

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, B, U, V, Z, W1, W2, W3, and R1-R6 are described herein.

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 Y1, X1, X2, Y2, W1, W2, W3, and R1-R5 are described herein.

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: (I) where Y1, X1, X2, Y2, W1, W2, W3, and R1-R5 are described herein.

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, B, U, V, Z, W1, W2, W3, and R1-R6 are described herein.

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, B, W1, W2, W3, and R1-R8 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 a test kit of auxiliary diagnosis of non-small cell lung cancer patients. The test kit comprises a product used for detecting protein landmark isocitrate dehydrogenase 1(IDH1), a product used for detecting protein landmark carbonic anhydrase 125 (CA125), a product used for detecting protein landmark CYFRA21-1 and a carrier on which a functional expression p=1 / (1+(20.186*0.406<x1>*0.923<x2>*0.656<x3>)<-1>) is recorded, wherein x1 represents the concentration of IDH1, x2 represents the concentration of CA125, and x3 represents the concentration of CYFRA21-1. The test kit is adopted and the non-small cell lung cancer patients are diagnosed in an auxiliary mode according to corresponding diagnosis standards, the test kit has the advantages of being high in sensitivity and strong in specificity, reliability of the diagnosis is far higher than that of diagnosis which is carried out with each single protein landmark, and the test kit has great value and application prospects for diagnosis and treatment of non-small cell lung cancer.

We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

The invention discloses a detection primer for human IDH (isocitrate dehydrogenase) gene mutation and a detection reagent kit, which are used for the combination of PCR (polymerase chain reaction) and high resolution melting curve analysis technique. The detection reagent kit can be used for detecting the gene mutation on IDH 1 and IDH2 gene exon 4, detection samples are human genomes DNA (deoxyribonucleic acid) extracted from tumor tissues, blood or bone marrow cells, and the detection reagent kit is used for patients with clinical brain glioma and hematopathy to assist tumor diagnosis, treatment and judging prognosis. The detection reagent kit is easy and rapid in operation and good in detection effect.

Provided are isocitrate dehydrogenase 2 (IDH2) inhibitor compounds useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof a compound described herein. Also provided are polymorphic forms of the IDH2 inhibitor compounds characterized by X Ray powder diffraction patterns, having improved physicochemical properties that influence in vivo dissolution rate for formulation purposes.

The invention belongs to the technical field of medical treatment and pyradiomics, and particularly relates to a gene heterogeneity visual quantification method in glioma based on pyradiomics and a system. The method of the invention comprises the steps of segmenting a glioma magnetic resonance image by means of an image segmenting network 3D U-net; performing predictive modeling on the integral glioma IDH (isocitrate dehydrogenase), namely performing high-flux characteristic extraction and characteristic screening on the image, and screening a characteristic combination which is most sensitive and most effective to gene expression; performing heterogeneous modeling on the glioma IDH based on an image block, extracting a multi-dimensional data block of the glioma image, obtaining the IDH expression strength of each data block based on the integral predicting model; and finally forming the IDH distribution visualization and quantitative expression of the whole tumor. The method and thesystem have advantages of more accurately determining the prognosis and radiotherapy and chemotherapy sensitivity of the patient, realizing surgery resection and targeting treatment in heterogeneous atlas navigation, and realizing high clinical value in improving treatment effect of the patient and improving survival prognosis.

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 belongs to the technical field of biomedicine and relates to an anti-tumor medicament based on alpha ketoglutaric acid and derivatives thereof. The derivatives comprise various ester derivatives, amide derivatives and ether derivatives; and the alpha ketoglutaric acid comprises chemical analogues and derivatives thereof. The results of in-vitro experiments indicate that the mutation of isocitrate dehydrogenase in gliomas results in the loss of enzyme activities, the alpha ketoglutaric acid capable of growing in cells is obvious reduced, the levels of anaerobic inductor factors capable of inducing tumors and promoting the growth of the tumors are obviously improved, and the phenomenon can be reversed by exogenously replenishing absorbable alpha ketoglutaric acid. Therefore, an absorbable alpha ketoglutaric acid compound can be used for treating the gliomas, pancreatic cancers, breast cancers, liver cancers, lung cancers, gastric cancers, colorectal cancers, colon cancer and melanomas.

The invention provides a (D)-2-hydroxyglutarate (D2HG) assay kit, which is prepared from sample processing chemical A (perchloric acid), sample processing chemical B (potassium hydroxide), reaction buffer (Tris-HCl), reaction substrates (coenzyme NAD, methyl thiazolyl tetrazolium MTT and electron transfer agent PMS), (D)-2-hydroxyglutarate dehydrogenase, a standard substance, a 96-pore microporousplate, and a microplate sealer. The optimal assayed concentration range of the kit for D2HG is 5mu M to 120mu M (0.96mu g / ml to 23mu g / ml). The kit disclosed by the invention has the characteristicsof easiness in operation, quickness, accuracy and high specificity, is suitable for assaying the concentration of D2HG in serum sample, and provides beneficial guidance for the clinical early diagnosis of patients with tumors related to isocitrate dehydrogenase (IDH) mutation, the determination of therapeutic strategies and prognosis evaluation.

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.

The invention discloses a double-aryl maleimide compound, pharmaceutically acceptable salt thereof, a method for preparing the double-aryl maleimide compound and the pharmaceutically acceptable salt and application of the double-aryl maleimide compound and the pharmaceutically acceptable salt. The double-aryl maleimide compound and the pharmaceutically acceptable salt can be particularly used as isocitrate dehydrogenase 1 (IDH1) mutant inhibitors and can be applied to treating malignant tumor such as glioma and acute myeloid leukemia. The double-aryl maleimide compound, the pharmaceutically acceptable salt, the method and the application have the advantages that the double-aryl maleimide compound has efficiently selective IDH1 mutant inhibitory activity, and accordingly the double-aryl maleimide compound and the pharmaceutically acceptable salt can be used for treating the IDH1 mutant mediated malignant tumor such as the glioma and the acute myeloid leukemia; the double-aryl maleimide compound, the pharmaceutically acceptable salt and the method are reasonable in design, and the method is simple and practical.

The invention relates to an anti-IDH1 R132H antibody as well as a preparation method and application thereof. The antibody or a functional derivative specifically identifies epitope of IDH1 R132H. The monoclonal antibody has (1) an amino acid sequence of a variable region of a heavy chain of antibody or a conservative variable sequence as shown in one of SEQ IDNO:2, 6, 10; and (2) amino acid sequence of a variable region of a light chain of antibody or a conservative variable sequence as shown in one of SEQ IDNO:4, 8, 12. The invention also relates to coded nucleic acid molecules, a construction vector, an expression system, a corresponding human source antibody, a preparation method, an application and a pharmaceutical composition. The antibody has immune specificity on human type I human isocitrate dehydrogenase (IDHI1)R132H, can specifically identify a mutant site of IDH1 R132H related to a malignant disease and is specifically combined therewith for diagnosing and treating diseases which have pathogenic effects after mutation of IDH1 R132H, for example, diseases such as glioma and leukemia.

The present invention relates to transgenic plants that have increased nitrogen use efficiency, stress tolerance, and / or alleviating a limitation such that yield is increased, or a combination of these and that have been transformed using a novel vector construct including a synthetic isocitrate dehydrogenase (icdh) gene that modulates nitrogen use in plants. The invention also relates to stacking the icdh gene with other exogenous or heterologous genes that modulate nitrogen use in the plant, including a N-acetylglutamate kinase gene. The invention also relates to methods of expressing in plants the nucleic acid molecules corresponding to the nucleic acid sequences that modulate nitrogen use in plants or are modulated by nitrogen conditions.

The invention relates to a compound of formula I shown in the description and its pharmaceutically salts, solvents and hydrates, as well as a pharmaceutical composition comprising the compound of formula I and application thereof as an IDH (isocitrate dehydrogenase 2) mutant inhibitor in the preparation of drugs for treating IDH mutation related diseases.

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 discloses a recombinant plasmid, including vectors and gene fragments. The gene fragments include pyridine nucleotide transhydrogenase gene containing promoters and isocitric dehydrogenase genes containing promoters. Compared with the prior art, the present invention has simple expression and purification process, the double promoter expression vector can not only provide possibility of right expression of protein difficult to express, but also can improve the output of the expressed protein with economic value, including pharmaceutical proteins and industrial enzymes, thereby reducing production costs and saving resources.

The invention relates to a recombinant strain of Bacillus subtilis, wherein pyruvate carboxylase BalpycA, glyceraldehyde-3-phosphate ferredoxin dehydrogenase gor, isocitrate NAD+ dehydrogenase icd, malate quinone dehydrogenase mqo, pyruvate ferredoxin oxidoreductase porAB and nitrogenase ferritin cyh are integrated and expressed in the recombinant strain. The invention also discloses use of the recombinant strain in fermentation production of acetylglucosamine. The recombinant Bacillus subtilis of the invention eliminates the central carbon metabolism overflow of the Bacillus subtilis and balances the intracellular reducing force, and the fermentation yield of acetylglucosamine is greatly improved.

The invention belongs to animal biology technology and breeding field of pigs, and particularly relates to cloning, activity analysis and promoter region mutation research of promoters of porcine isocitrate dehydrogenase genes IDH3beta. The method comprises the following steps of: extracting genomes DNA from porcine blood, designing primers, obtaining genome base sequences of upstream 5' flank 2447bp of porcine IDH3beta genes in two-time amplification mode by adopting TAIL-PCR technology, and performing sequence comparison and analysis and genetic variation detection; and amplifying the upstream 5' flank region of the IDH3beta genes by adopting 5'-end deletion strategy, constructing luciferase report gene vectors by using the obtained DNA sequences, measuring the activity of the promoters, and identifying the promoters of the IDH3beta genes. The nucleotide sequences of the promoters of the cloned porcine isocitrate dehydrogenase genes IDH3beta are expressed as sequence tables SEQ ID No: 1 and SEQ ID No: 4. The invention provides gene resources for porcine genetic improvement application.

The invention relates to a kit for diagnosing 5'-nucleotidase by utilizing the technologies of the enzymic colorimetry and the enzyme linked immunosorbent assay. The invention further relates to a method, a principle and the composition and the components of a reagent for measuring the active concentration of 5'-nucleotidase, and belongs to the technical field of medical inspection and measurement. The main components of the kit include a buffer solution, reduced coenzyme, nucleoside monophosphate, adenosine diphosphate, an oxaloacetic acid, a ketoglutaric acid, pyruvate carboxylase, isocitrate dehydrogenase and a stabilizer. Through mixing a sample and the reagent by a certain volume ratio, a series of enzymatic reactions occur, then the reactant is placed under an ultraviolet / visible light analyzer, and the velocity of the decrease in absorbance at 340 nm of the dominant wavelength is detected, thereby measuring the active concentration of 5'-nucleotidase.