26 results about "Glucose transporter" patented technology

The invention discloses selenoglycoside gligliflozin as well as a preparation method and application thereof. The structural formula of the selenoglycoside gligliflozin disclosed by the invention is shown as a formula (I). The preparation method of the seleno-glucoside gliflozin comprises the following steps: 1, directly carrying out selenium-carbon coupling reaction on peracetyl-protected 1-seleno-glucose in a solvent under the action of alkali and a palladium catalyst to prepare tetra-acetyl-protected seleno-glucoside gliflozin; and step 2, carrying out deacylation on the tetra-acetyl protected seleno-glucoside gliliflozin product to prepare the seleno-glucoside gliliflozin. A biological activity test shows that the selenoglycoside gliliflozin provided by the invention shows low toxicity to cells, high inhibitory activity to SGLT-2 (sodium glucose transporter 2) and beta-glucosidase hydrolysis resistance, so that the selenoglycoside gliliflozin has the potential to be developed into a medicine for treating diabetes mellitus 2. (I)

The present invention relates to a crystalline form of a glucopyranosyl derivative and its use. In particular, the present invention relates to a crystalline form of N-(2-dimethylaminoethyl)-1-[4-[4-[[5-[(2S,3R,4S,5S,6R)-6-ethyl-3,4,5-trihydroxy-tetrahydropyran-2-yl]-2-methyl-phenyl]methyl]phenyl]butyrylamino]cyclohexylformamide and a pharmaceutical composition comprising the crystalline form, and further to the use of the crystalline form and the pharmaceutical composition in the preparation of a sodium-dependent glucose transporter (SGLT) inhibitor.

The invention relates to the technical field of pharmaceutical preparations, in particular to mRNA (messenger ribonucleic acid) lipid nanoparticles and application thereof in treatment of triple-negative breast cancer. The invention constructs an mRNA lipid nanoparticle, breaks through the dilemma of single drug curative effect of a glucose transporter (GLUT) inhibitor and a glutaminase (GLS) inhibitor for triple negative breast cancer, and realizes double-track treatment of mRNA metabolism reprogramming and small molecule energy deprivation for the first time. The mRNA lipid nanoparticles enhance the sensitivity of triple negative breast cancer to small molecule energy deprivation treatment, so that the clinical transformation feasibility of BAY-876 and CB-839 is improved to a new dimension. The delivery efficiency of the mRNA lipid nanoparticles is high, the biological safety is good, meanwhile, the production process of the nanoparticles is simpler and more standard compared with plasmids and viruses, and the drug production cost is lower.

Disclosed herein are methods of treating and ameliorating hyperinsulin hypoglycemia using sodium dependent glucose transporter (SGLT) 1 inhibitor compounds and compositions comprising them.

The invention discloses an FSTL1 overexpression adeno-associated virus and application thereof, and aims to efficiently deliver a mouse source FSTL1 gene into mouse muscle cells by virtue of a virus infection mechanism by utilizing the targeting property of AAV1 type to muscle tissues. FSTL1 is overexpressed in mouse muscle tissue, muscle insulin signal transduction and glucose metabolism processes are adjusted from multiple dimensions of insulin signal channel activation, glucose transporter regulation and control and the like, and therefore the insulin sensitivity and glucose metabolism conditions of muscles in an obese mouse model are improved.

The present invention provides a glucose transporter (GLUT)-based lysosome targeting chimera. The lysosome targeting chimera can effectively enrich and degrade in lysosomes different types of target proteins on the cell surface and outside the cell. The present invention further provides an application of the lysosome targeting chimera, and an antibody-drug conjugate obtained by conjugating the lysosome targeting chimera with a cytotoxic drug.

The present invention relates to a key intermediate for preparing a glucopyranosyl derivative, which is a sodium-dependent glucose transporter (SGLT) inhibitor, and a preparation method thereof. Specifically, the key intermediate provided by the present invention has stable properties, few impurities, and high optical purity (diastereoselectivity). The preparation method provided by the present invention utilizes inexpensive reagents, mild reaction conditions, does not require silica gel column chromatography purification, is simple to post-process, is easy to purify, has low equipment requirements, low production costs, and a safe and controllable process, making it suitable for industrial production.

The invention discloses a blood-brain barrier crossing nucleic acid drug delivery system based on glycosyl functional nucleic acid and a preparation method and application thereof, and belongs to the technical field of biomedicine. The core of the system is a glycosylated transferrin receptor aptamer (GTA), and the GTA is formed by covalently linking a glycosyl modification module and a transferrin receptor binding sequence and can be combined with therapeutic nucleic acid to form a compound. According to the invention, the blood-brain barrier crossing efficiency and brain targeting property of nucleic acid drugs are remarkably improved through a dual-channel synergistic mechanism formed by transferrin receptor mediated transfection and glucose transporter assisted uptake; the GTA can be automatically prepared through a DNA solid-phase synthesis platform, and is controllable in structure, stable in batch, high in biocompatibility and low in immunogenicity. The delivery system can be compatible with multiple nucleic acid drugs such as siRNA, ASO and CpG ODN, and has a wide application prospect in treatment of central nervous system diseases such as glioblastoma.

The application discloses application of a glucose transporter 1 inhibitor in preparation of a drug for treating diabetic neuropathy. The application verifies that the glucose transporter 1 inhibitor BAY-876 can be used as a drug for treating diabetic peripheral neuropathy and can be combined with mecobalamin to be used as a drug for treating diabetic peripheral neuropathy through pharmacodynamics experiments.

The invention relates to application of trichocephalus microcoleus in production of GG and construction of engineered trichocephalus microcoleus with high yield of GG. According to the method disclosed by the invention, engineered coleus microcoleus with high yield of GG is constructed, and culture conditions for synthesizing glycerol glucoside by the coleus microcoleus BL0902 are optimized. Glycerin and glucose are added into the culture medium at the same time, so that the GG yield is improved to the optimal degree, and the GG yield is improved by about 4 times. Through overexpression of gtr, ggpS and ggpP, carbon flow is promoted to enter a path for synthesizing glycerol glucoside. The result shows that the total GG yield of the gtr-overexpressed algal strain is increased from 193.6 mg / L to about 337 mg / L 24 hours after the gtr-overexpressed algal strain is externally added with glycerol and glucose. On the basis, the ggpS and the ggpP are further overexpressed, and the total GG yield of the algae strain is increased to about 984.7 mg / L. In conclusion, the key genes ggpS and ggpP synthesized by overexpressing the glucose transporter gene gtr and GG, the GG yield is remarkably increased and can reach 984.7 mg / L to the maximum, and the yield is 393.88 mg / L / d.

The invention provides a pharmaceutical composition helpful for reducing blood glucose as well as a preparation and application thereof, and relates to the field of medicines. The pharmaceutical composition helpful for reducing blood glucose comprises the following raw materials in parts by weight: 15-20 parts of pomegranate, 8-13 parts of turmeric, 1-2 parts of bear gall, 1-2 parts of schisandra chinensis, 10-15 parts of dendrobe, 5-10 parts of folium eriobotryae, 8-12 parts of radix puerariae, 5-10 parts of dandelion, 8-15 parts of herba epimedii, 8-12 parts of polygonum cuspidatum, 5-8 parts of gynostemma pentaphyllum, 4-8 parts of inula flower and 3-5 parts of cortex lycii radicis. The pharmaceutical composition disclosed by the invention effectively inhibits sugar absorption of intestinal tracts, enhances insulin sensitivity, improves insulin resistance, promotes activity of glucose transporter protein, regulates glycolipid metabolism balance, inhibits liver glycogen decomposition to reduce liver glucose output and reduces interference of inflammatory factors on insulin signal channels through a multi-channel synergistic effect; therefore, the whole metabolic regulation is optimized, the blood sugar level is remarkably reduced, the number of pancreatic beta cells is increased, and the compound can be applied to preparation of drugs for treating diabetes.

The present disclosure relates to a combination therapy for treating cancer comprising belinostat or a pharmaceutically acceptable salt, tautomer, stereoisomer, mixture of stereoisomers, prodrug, or deuterated analog thereof and at least one glucose transporters (GLUT) inhibitor. Belinostat and the GLUT inhibitor can either be administered separately or in the form of a single composition. Thus, the disclosure relates to a kit comprising Belinostat and at least one GLUT inhibitor, wherein Belinostat and the GLUT inhibitor are in separate formulations and, alternatively, to a composition comprising belinostat and at least one GLUT inhibitor, such as a pharmaceutical composition. It also relates to such kit or such composition for use in the treatment of cancer, preferably for the treatment of lymphoma(s).

The invention relates to a construction and fermentation method of recombinant corynebacterium glutamicum for high-yield indigoidine, and the recombinant corynebacterium glutamicum is obtained by taking corynebacterium glutamicum as an original strain and transforming one or more of A-D items; the method comprises the following steps: A, knocking out a gene for coding glucose transporter on a genome, and integrating a glucose permease gene and a glucokinase gene; b, knocking out a gene for coding gamma-glutamyl kinase on a genome, and integrating a glk gene at the same time; c, overexpressing an ornamental blue synthetase gene and a 4 '-phosphopantetheinyl transferase gene; and D: overexpressing a glutamine synthetase gene, an alpha-ketoglutarate dehydrogenase inhibiting enzyme gene, a glutamate dehydrogenase gene and an isocitrate dehydrogenase gene. According to the method, glutamine can be efficiently converted, the yield of the indigoidine is greatly increased, and a foundation is laid for industrial production of the indigoidine.

The invention discloses a glucose metabolism reconstruction-based engineering strain for efficiently synthesizing rhamnolipid and a construction method thereof, the construction method comprises the following steps: taking pseudomonas putida KT2440 or a flag gene cluster knockout strain thereof as an original strain, optimizing the genome of the original strain through gene modification, and introducing recombinant plasmids to obtain the engineering strain for efficiently synthesizing rhamnolipid; the modification comprises at least one of (1) to (6): (1) heterologous expression of rhamnolipid synthesis related genes; (2) replacing the rmlA gene with the gene rmlA *; (3) knocking out related genes for coding Gad; (4) heterologous expression of a galP gene encoding glucose transporter protein; (5) heterologous expression of the glf gene encoding the glucose transporter; and (6) overexpressing and coding the glk gene of glucokinase. The method disclosed by the invention has the beneficial effects that efficient directional distribution of glucose to a rhamnolipid synthesis route is realized, and the synthesis efficiency of the rhamnolipid is remarkably improved.

Provided herein are compositions, kits, and methods for manufacturing cells for treating or regenerating damaged or diseased tissue comprising engineered fibroblasts, myoblasts, osteocytes, chondrocytes, adipocytes, epithelial cells, or mesenchymal stem cells that overexpress glucose transporter 5 (GLUTS).

The invention relates to a preparation method of a photoacoustic nanoprobe for targeted recognition of M1 type macrophages. The preparation method comprises the following steps: S1, synthesizing a small molecular compound c responding to nitric oxide; s2, preparing the photoacoustic nanoprobe Lipo-atNM-Glu for targeted recognition of M1 type macrophages, the probe is endowed with functions of in-vivo targeted M1 type macrophage surface overexpression of glucose transporter and selective response of M1 type macrophage biomarker-nitric oxide and the like, so that the ability of the probe for targeted recognition of M1 type macrophages is improved; further, the sensitivity and the specificity of in-vivo photoacoustic imaging of the M1 type macrophages are improved.

The invention relates to bacillus subtilis for producing D-psicose and application of the bacillus subtilis, and belongs to the technical field of microorganisms. The invention discloses a recombinant bacillus subtilis obtained by performing gene editing by using a CRISPR / Cpf1 system, a D-psicose 6-phosphoric acid 3-epimerase coding gene A6PE, a glucokinase coding gene glck and a glucose transporter coding gene glf are integrally expressed in a starting bacillus subtilis genome, and a 6-phosphofructokinase coding gene pfkA is knocked out, so that the recombinant bacillus subtilis is obtained. A metabolic pathway for producing D-psicose by taking glucose as a substrate is constructed in bacillus subtilis, and the production efficiency is improved in a form of enhancing glucose uptake and conversion capacity, so that the yield of D-psicose of the constructed recombinant bacillus subtilis at a 250 mL shake flask fermentation level reaches 23 g / L. The bacillus subtilis for producing D-psicose provided by the invention has the advantages of directional regulation and control of metabolic flux, high substrate utilization rate, low production cost and the like, and is suitable for industrial production.

The subject matter of the present disclosure generally relates to techniques for neuromodulation that include applying energy (e.g., ultrasound energy) into the tissue to cause a change in a glucose transporter pathway molecule and / or an incretin pathway molecule. In one embodiment, the neuromodulation is performed as a treatment of a metabolic disorder.

The invention provides a composition for reducing a glycemic index and application of the composition, and belongs to the technical field of functional foods and health-care products. The composition provided by the invention comprises the following components in parts by weight: 15-68 parts of branched chain amino acid (BCAA) and 0.1-6 parts of taurine. The branched chain amino acid and the taurine in the composition can protect pancreatic beta cells, promote insulin secretion and improve insulin resistance, insulin sensitivity, expression and translocation of glucose transporters and the like. In addition, the branched chain amino acid in the composition can enable insulin to recover to a normal level, and normal secretion and carbohydrate homeostasis of the insulin of the body are guaranteed. The composition disclosed by the invention can reduce the glycemic index from multiple dimensions, also can ensure the absorption of high protein and the intake of high-quality carbonated water, is more beneficial to the simultaneous intake of multiple nutrients by an organism, and maintains the health of the organism.

This invention discloses dehydroascorbic acid-modified hemoglobin-based Paris polyphylla saponin-targeted nanoparticles and their preparation method, belonging to the field of drug delivery system technology. These targeted nanoparticles use hemoglobin as a drug carrier and Paris polyphylla saponin VII as the core active ingredient. The process involves first synthesizing a DSPE-PEG-DHA polymer, then utilizing the property of Hb exposing its hydrophobic region under acidic conditions to encapsulate PSVII within Hb via a self-assembly method, and finally modifying it with DSPE-PEG-DHA to obtain the target nanoparticles PSHb@DPD. This invention significantly enhances the targeting and cellular uptake efficiency of nanoparticles by specifically binding DHA to glucose transporters highly expressed in osteosarcoma cells. It exhibits strong toxicity to osteosarcoma MG63 cells and effectively inhibits their migration, while showing no significant toxicity to normal vascular endothelial cells and excellent biocompatibility.

The invention relates to a lipid nanoparticle for targeted co-delivery of a gene drug and an immune agonist and application of the lipid nanoparticle in treatment of PTEN deletion type brain glioma. A glycosylated polyethylene glycol lipid compound DMG-PEG-Glu is designed and constructed; the glucose (ligand) modified lipid nanoparticles CP-GLNPs for brain-targeted co-delivery of PTEN mRNA (gene drug) and cGAMP (immune agonist) can be prepared from glucose (ligand) modified lipid nanoparticles CP-GLNPs with ionizable lipid, cholesterol and auxiliary lipid. According to the invention, LNP co-delivery of PTEN mRNA and cGAMP is realized for the first time, the size is in a hundred-nanometer level, and the glucose transporter 1 highly expressed on the surfaces of brain endothelial cells and tumor cells can efficiently enter the brain to play a role through a blood-brain barrier. The invention realizes the breakthrough of a nucleic acid drug and immune agonist co-delivery technology, and is a novel nano-drug delivery system for treating both symptoms and root causes of gene therapy and immunotherapy.

A method produces rhamnolipids by contacting a cell with a medium containing a carbon source, culturing the cell under conditions allowing the cell to make rhamnolipids from the carbon source, and optionally isolating the rhamnolipids made, wherein the cell is a rhamnolipid-making cell that it is genetically modified such that it has a decreased activity, compared to the wild type thereof, of an ABC glucose transporter and an increased activity, compared to the wild type thereof, of at least one non-ABC glucose transporter.

The invention relates to application of a specific inhibitor BAY-876 targeting glucose transporter 1 in prevention and treatment of hypoglycemia. The hypoglycemia is at least one of diabetic hypoglycemia, non-diabetic hypoglycemia and recurrent hypoglycemia. The invention also provides a medicine for preventing and / or treating at least one disease of diabetic hypoglycemia, non-diabetic hypoglycemia and recurrent hypoglycemia. Meanwhile, the invention further provides application of the BAY-876 in preparation of drugs capable of improving the fasting glucagon level of a diabetic individual and / or a non-diabetic individual in vivo and / or maintaining fasting blood glucose stability in vivo and / or improving diabetic hypoglycemia and non-diabetic hypoglycemia in vivo. The invention also relates to application of the medicine or the reagent for reverse regulation of at least one disease in recurrent hypoglycemia. In conclusion, the invention provides a new means for developing medicines for preventing and / or treating at least one disease of diabetic hypoglycemia, non-diabetic hypoglycemia and recurrent hypoglycemia.

The invention discloses recombinant corynebacterium glutamicum for high yield of N-acetylglucosamine, which is characterized in that corynebacterium glutamicum ATCC13032 is used as an original strain; an N-acetylglucosamine-6-phosphate deacetylase encoding gene nagA, a glucosamine-6-phosphate deaminase encoding gene nagB, a glucose-6-phosphate 1-dehydrogenase encoding gene zwf, a lactic dehydrogenase encoding gene ldhA, an N-acetylmannosamine-6-phosphate 2-epimerase encoding gene nano E, a glucosamine-6-phosphate deacetylase encoding gene nagA, a glucosamine-6-phosphate deacetylase encoding gene nagB, a glucose-6-phosphate 1-dehydrogenase encoding gene zwf, a lactic dehydrogenase encoding gene ldhA, a lactic dehydrogenase encoding gene ldhA, a an N-acetylglucosamine specific phosphotransferase encoding gene cgl2642 and a glucose transporter encoding gene ptsG are used as the specific gene of the N-acetylglucosamine specific phosphotransferase; the invention also discloses a method for preparing the recombinant glucosamine-6-phosphate acetyltransferase gene, and expresses an exogenous glucosamine-6-phosphate acetyltransferase coding gene GNA1, an exogenous glutamine-fructose-6-phosphate transaminase coding gene glmS, an exogenous glucose transporter coding gene galP and an exogenous glucose transporter coding gene glf.

Provided herein are compositions, kits, and methods for manufacturing cells for treating or regenerating damaged or diseased tissue comprising engineered fibroblasts, myoblasts, osteocytes, chondrocytes, adipocytes, epithelial cells, or mesenchymal stem cells that overexpress glucose transporter 5 (GLUTS).

The invention belongs to the technical field of bioengineering, and relates to a recombinant engineering bacterium and application thereof in preparation of mannitol, and the recombinant engineering bacterium is a plasmid-free strain for producing a cofactor NAD < + > by using cheap xylose and nicotinamide. The following genes are knocked out from the strain: a gene ptsG for coding protein EIICBGlc in a glucose PTS system, mtlA for coding EIICA protein in D-mannitol transmembrane transport, a D-mannitol 1-phosphate dehydrogenase gene mtlD in a D-mannitol utilization path, purine de novo synthesis regulation protein purR, and srlAE in a sorbitol utilization gene cluster. The following genes are integrated in a genome of the strain: glucose transport assisting protein glf, glucokinase glcK, xylose utilization gene cluster xylose isomerase xlyA and xylulose phosphorylase xlyB, phosphoribose pyrophosphate synthetase prs, polyphosphate kinase ppk2, nicotinamide phosphoribose transferase nadV and nicotinamide mononucleotide adenylate transferase nadM. The strain is fermented by using glucose and xylose, and provides chassis bacteria for reaction needing cofactor circulation.