51 results about "Limonoate dehydrogenase" 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, 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, 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, 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 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, 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, 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.

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 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 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 an isocitrate dehydrogenase kinase mutant and application of the isocitrate dehydrogenase kinase mutant in preparation of aromatic amino acid. The sequence of an isocitrate dehydrogenase kinase mutant gene aceK is shown as SEQ ID No. 1. The constructed engineering bacterium containing the escherichia coli coded isocitrate dehydrogenase kinase mutant gene aceK is biologically safe and clear in genetic background, the capacity of escherichia coli for producing aromatic amino acid can be effectively improved, and the yield of phenylalanine and the yield of tryptophan are increased by 12.1% and 11.1% respectively.

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 present invention is directed to a method utilizing a microorganism with reduced isocitrate dehydrogenase activity for the production of fine chemicals. Said fine chemicals may be amino acids, monomers for polymer synthesis, sugars, lipids, oils, fatty acids or vitamins and are preferably amino acids of the aspartate family, especially methionine or lysine, or derivatives of said amino acids, especially cadaverine. Furthermore, the present invention relates to a recombinant microorganism having a reduced isocitrate dehydrogenase activity in comparison to the initial microorganism and the use of such microorganisms in producing fine chemicals such as aspartate family amino acids and their derivatives.

The present invention discloses a high-temp. resistant isocitrate dehydrogenase gene, its coded polypeptide and its preparation method. It relates to coding separated DNA with activity and its functional identification variant and utilizing the recombinant DNa technique and using the described separated DNA to produce polypeptide with high-temp. resistant isocitrate dehydrogenase activity or its functional identification variant. This invention uses tengchaong thermophilic anaerobe hologenome sequencing and analysis as basis to clone and separate a kind of high-temp. resistant isocitrate dehydrogenase gene, and the said gene can be used for producing a transgenic microbe or animals or plant of high-temp. resistant isocitrate dehydrogenase, and recovering the enzyme coded by the said gene.Besides, this invention also provides amino acid sequence of polypeptide with high-temp. resistant another isocitrate dehydrogenase activitity and its functional identification body, and also provides the preparation, separatino and purification processes of the said polypeptide.

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 pertains to the porcine marker-assisted selection technical field. A genetic mark which is suitable for detecting porcine productive trait is cloned by the invention. The genetic mark is porcine isocitric acidcitric dehydrogenase gene IDH3Gamma, and cDNA sequence of the gene is stated in sequence table SEQID NO: 1. the sequence length is 1346bp, containing an open reading frame of 1179bp, an untranslated region of 36bp5' and a 3' untranslated region of 131p. The nucleotide sequences of IDH3Gamma gene such as SEQID NO: 3, SEQID NO: 4, SEQID NO: 5 and SEQID NO: 6 contain a second intron sequence of IDH3Gamma, and provide a new genetic mark the porcine marker-assisted selection. The invention also discloses a cDNA sequence of porcine IDH3Gamma gene and DNA sequence of the second intron for application of the pig microsatellite typing test.

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 compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

The invention discloses an enzyme activity detection kit for alpha-oxoglutarate dependent enzyme and an application thereof. The kit includes one of reduced coenzyme II (NADPH) or reduced coenzyme I (NADH), an isocitrate dehydrogenase IDH mutant protein and buffer salt, and the IDH mutant protein refers to an IDH mutant protein having a novel function of catalyzing alpha-oxoglutarate (2-OG) obtained after mutation of a specific amino acid of IDH. As a preferred scheme, the kit further includes a metal ion that competes for ferrous ions. The invention provides a method for detecting the contentof the alpha-oxoglutarate with high efficiency and high precision, which can be used for detecting the enzymatic activity of alpha-oxoglutarate dependent enzyme, determining the enzyme kinetic parameters, and performing high-throughput drug screening by targeting the type of enzyme. The method solves the problems of complex operation, low accuracy, reproducibility, low flux, and difficulty in screening high-throughput drugs for the enzyme activity detection of the alpha-oxoglutarate dependent enzyme.

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.