39 results about "GLUT1" patented technology

The present disclosure provides methods of treating an inflammatory skin disease (e.g., psoriasis) in a subject by administering an inhibitor of Hypoxia Inducible Factor 1α (HIF1α) or an inhibitor of glucose transporter 1 (Glut1). The present disclosure also provides topical formulations comprising an inhibitor of HIF1α or an inhibitor of Glut1.

The present invention discloses a targeted knockout bovine FGFR1 The application of the sgRNA of the gene in constructing a bovine mammary epithelial cell line, wherein the sgRNA nucleotide sequence is shown in SEQ ID NO: 1. The mammary epithelial cell line obtained by constructing the sgRNA of the present invention through CRISPR / Cas9 technology, FGFR1 Protein expression was significantly downregulated, and knockout FGFR1 The gene expression had no significant effect on the viability and proliferation of mammary epithelial cells. PCNA 、 Cyclin D1 、 Cyclin E1 There was no significant change in the mRNA expression of the genes related to milk protein synthesis (such as CSN1S1 、 CSN2 、 CSN3 、 EFL5 ), lactose synthesis-related genes ( GLUT1 and HKⅡ ) and milk fat synthesis-related genes ( SCD‑1 ) were significantly decreased, providing a basis for in-depth analysis FGFR1 It provides key tools for the regulatory mechanisms of mammary epithelial cell proliferation, lactation synthesis and other biological behaviors.

The invention discloses application of an HIF1A inhibitor in preparation of a medicine for preventing and / or treating hypertrophic cardiomyopathy, and belongs to the field of biological medicine. For a rat model of spontaneous hypertrophic cardiomyopathy caused by MYH7B gene knockout, hypertrophic cardiomyopathy can be significantly relieved by intraperitoneal injection of the HIF1A inhibitor LW6, heart remodeling can be relieved, heart functions can be improved, and myocardial hypertrophy caused by silent MYH7B genes can be effectively resisted by using siRNA of mRNA transcribed by the HIF1A gene. The key mechanism of the HIF1A inhibitor for treating the hypertrophic cardiomyopathy is that the hypertrophic cardiomyopathy is prevented and treated by reducing the expression level of glycolysis key enzymes GLUT1, HK2 and the like, inhibiting the formation and accumulation of cardiac lactic acid and improving the ventricular remodeling of the hypertrophic cardiomyopathy. The results show that the HIF1A inhibitor can be used for treating and / or preventing the human hypertrophic cardiomyopathy and has the potential of being developed into the medicine for clinically preventing and treating the hypertrophic cardiomyopathy.

The invention discloses a glucan-based MMAE conjugate as well as a preparation method and application thereof, and relates to the technical field of medicines. The conjugate takes glucan with good biocompatibility as a carrier, and is covalently connected with a cytotoxic drug MMAE through a VC peptide linker capable of being cut by cathepsin B. The conjugate has good serum stability, can specifically release drugs at a tumor site, and realizes efficient tumor uptake by virtue of the stealth effect of glucan and potential GLUT1 targeting. In-vitro and animal experiments show that the conjugate has a remarkable treatment effect on pancreatic cancer and is low in systemic toxicity.

The present invention belongs to the field of medicinal chemistry and relates to a triazine-thiazolidinone compound and its preparation method and application. Its structural formula is wherein R1 is any one of alkyl, pyranyl, indolyl, phenyl or thienyl. Its pharmaceutically acceptable salt is the acid salt of the compound, and the acid is any one of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, boric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, benzenesulfonic acid, citric acid, lactic acid, pyruvic acid, tartaric acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, salicylic acid or phenylacetic acid. The triazine-thiazolidinone compound skeleton provided by the present invention is novel, has a good inhibitory effect on glucose transporter 1 (GLUT1), and its inhibitory effect in HT29 cells is much better than that of positive control compound BAY-876, with good potential for further development as an anti-tumor drug.

A nucleic acid construct encoding glucose transporter 1 or mitochondrion transcription factor A, and a vector or a cell containing such a nucleic acid construct are provided. An engineered T cell overexpressing GLUT1 and / or TFAM is also provided. Also provided are methods for reducing viability and / or proliferation of an AML cell by contacting the AML cell with the engineered T cell composition, as well as methods for treating AML in a subject by administering the subject the engineered T cell composition.

A PAMAM-based protein degradation system and a method of preparation and use thereof are provided. The protein degradation system comprises: a silica nanoparticle core; and a poly(amidoamine) dendrimer (PAMAM) layer coated on a surface of the silica nanoparticle, wherein the PAMAM layer is linked via amide bonds to three small-molecule ligands: MDM2 protein ligand Idasanutlin, GLUT1 protein ligand Lavendustin B and E3 ubiquitin ligase ligand Thalidomide-NH—CH2—COOH. The nanoparticle protein degradation system cooperatively degrades MDM2 protein and GLUT1 protein. This cooperative degradation strategy not only effectively suppresses proliferation and energy metabolism of tumor cells, but also significantly enhances the stability of p53 protein. By restoring the normal function of p53 protein, tumor cell growth is further inhibited, providing a new strategy for cancer therapy.

The present invention discloses a dual-targeting molecule based on hyaluronic acid and glucose, a preparation method and application thereof, in particular, a dual-targeting fluorescent probe and anti-tumor drug based on hyaluronic acid and glucose. The dual-targeting fluorescent probe utilizes the interaction between HA-CD44 and Glc-GLUT1 to simultaneously target the CD44 and GLUT1 receptors of tumors (e.g., lung tumors), and can deliver fluorescent molecules into tumor cells in a targeted manner, reducing the aggregation of fluorescent molecules in normal cells; at the same time, the tumor cell endocytosis efficiency of fluorescent molecules can be improved. The chemical structures of the two targeting molecules HA and glucose in the dual-targeting fluorescent probe are clear, and the covalent bond connection sites and compositions are clear. This feature provides dual-targeting molecules with very good research and application value in drug delivery system applications and innovative drug development.

The application discloses application of aurantiamarin in preparation of a GLUT1 protein targeting inhibitor with high affinity, and belongs to the technical field of medicinal chemistry. It is found that aurantiamarin shows micromolar (muM) level high-efficiency inhibitory activity on GLUT1, and the aurantiamarin may play a role through a new mechanism different from existing competitive inhibitors, such as allosteric inhibition or state-dependent blockage, effectively blocks glucose uptake, and is not prone to drug resistance.

The present invention relates to a novel antisense transcript to the human SLC2A1 (Glut1) gene, variants and fragments thereof. This antisense transcript can be used to modulate Glut1 expression and serve to restore Glut1, and as a therapeutic for treating or preventing Glut 1 deficiency syndrome, or other Glut1 related conditions including certain cancers, diabetes, Alzheimer's disease, and retinitis pigmentosa.

The invention discloses a metabolic antagonist solution which is obtained by dissolving a metabolic antagonist in water, the metabolic antagonist is L-2-enol hexolactone and / or 2-deoxy-D-glucose, and the invention also discloses an application of the metabolic antagonist solution in storage of crude rosin. The metabolism antagonist solution provided by the invention aims at glycolysis and energy metabolism of impurities such as pine needles and barks, and discoloration and degradation of the crude rosin in the storage process are blocked from the source; the L-2-enol hexanoic acid lactone oxidation product enters cells through glucose transporters such as GLUT1 / 3 / 4, competes for binding sites with glucose, and interferes with glycolysis and energy metabolism of impurities such as pine needles and barks; the 2-deoxy-D-glucose has a pyranoid ring conformation highly similar to that of glucose, is acidified into 2-deoxyglucose-6-phosphoric acid by hexokinase, and hijacks a glycolytic pathway, resulting in metabolic blocking and energy depletion.

The invention belongs to the technical field of drug carriers, and particularly relates to tumor-targeted luteoloside liposome loaded paclitaxel and a preparation method thereof. According to the tumor targeted liposome, luteoloside and soya bean lecithin are used as membrane materials, a blank liposome (C-Blank) is prepared through a membrane hydration method and a high-pressure homogenization method, and a hydrophobic drug paclitaxel (PTX) is loaded to obtain a drug-loaded liposome (C-PTX). Wherein the luteoloside can significantly enhance the mechanical strength and thermodynamic stability of the lipid bilayer, and also can realize active tumor targeting through a glucose transporter GLUT1 mediated endocytosis pathway, and meanwhile, PTX is efficiently entrapped in a liposome hydrophobic core. The C-PTX liposome prepared by the invention is small in particle size, relatively good in endocytosis capability, good in blood long-circulation effect and drug delivery capability, good in stability and dispersity, high in drug encapsulation efficiency and beneficial to effective delivery and release of drugs. The oral bioavailability of PTX is improved, and C-PTX has an obvious inhibition effect on lung cancer cells. The drug loading system effectively overcomes the defects that a traditional paclitaxel preparation is poor in water solubility, large in system toxicity, insufficient in targeting performance and the like, the highly-uniform dispersion state and long-term storage stability of the drug loading system lay a foundation for industrial production, and the drug loading system shows important clinical application potential in the fields of precision medicine and transformation medicine.

The invention discloses a preparation method and application of glucose transporter 1 targeting brucea javanica fatty acid prodrug liposome, and belongs to the technical field of pharmaceutical preparations. Specifically, the invention relates to a targeting material based on glucose transporter 1 (GLUT1), a tumor sensitive bond bridged brucea javanica-fatty acid prodrug, construction of an active targeting liposome containing the prodrug, and application of the active targeting liposome in preparation of antitumor drugs. The anti-liver cancer effect of the liposome is investigated. Results show that the lipidosome designed by the invention can realize targeted drug delivery to tumor tissues, the anti-tumor efficacy of the brucea javanica terpene drug is remarkably improved, the biosafety is high, and the toxicity is reduced by two times compared with that of the original drug brucea javanica bitter alcohol. The tolerance dose of the chemotherapeutic drug is expected to be increased, the anti-tumor effect of the chemotherapeutic drug is improved, and a new direction and a new thought are provided for the delivery of the chemotherapeutic drug.

Anti-SLC2A1 antibodies and binding fragments thereof are disclosed. The antibodies and fragments are useful for inhibiting glucose uptake in tumor cells and for reprogramming tumor cell metabolism to oxidative phosphorylation. The disclosed antibodies and binding fragments thereof are suitable for cancer treatment alone or in combination with compounds that inhibit the oxidative phosphorylation pathway.

Provided herein are methods of stratifying oral lesions based on the risk of progressing into a malignant tumor, and methods of treating subjects involving selective removal of oral lesions identified as high risk. In some aspects, the methods provided herein include assessing risk based on expression of SLC2A1 on a lesion.

The invention discloses a targeting vesicle based on M1 type macrophage metabolism design as well as preparation and application of the targeting vesicle. The targeting vesicles are glucose modified macrophage membrane vesicles, the protein concentration is 2 mg / mL, and the mass ratio of a macrophage membrane to glucose is (10-20): 1. Glucose is a glucose derivative molecule capable of being recognized by GLUT1 or a homologous transporter of GLUT1, and is modified to the surface of a macrophage membrane through membrane insertion, physical adsorption, click chemical reaction, amido bond formation or Michael addition, so that the binding capacity of the vesicles and M1 type macrophages highly expressing GLUT1 and other glucose transporters can be improved. The targeting vesicles are used for loading anti-inflammatory metabolites, anti-inflammatory small molecule drugs or siRNA, targeting intervention drugs under different disease models can be prepared according to different biological membrane sources, pathological microenvironments and drug loading, and the targeting vesicles are suitable for various clinical scenes such as inflammatory diseases, tumor metabolism regulation and control, tissue repair and the like.

The present invention relates to a novel antisense transcript to the human SLC2A1 (Glut1) gene, variants and fragments thereof. This antisense transcript can be used to modulate Glut1 expression and serve to restore Glut1, and as a therapeutic for treating or preventing Glut 1 deficiency syndrome, or other Glut1 related conditions including certain cancers, diabetes, Alzheimer's disease, and retinitis pigmentosa.

The application provides an application of PTN and an extracellular vesicle loaded with PTN in preparation of a medicine for treating diabetic nephropathy, and belongs to the technical field of biological medicine; the application finds and confirms that small extracellular vesicles derived from human umbilical cord mesenchymal stem cells interact with glucose transporter 1 (GLUT1) in renal tubular epithelial cells through the multi-effect protein (PTN) carried by the small extracellular vesicles and down-regulate the expression of the glucose transporter 1, so as to inhibit abnormal aerobic glycolysis induced by high glucose, reduce lactic acid accumulation, and then repair the damage of diabetic nephropathy by reducing the lactic acid level; the application further verifies the role of PTN in the repair of the damage of diabetic nephropathy, and compared with a broad-spectrum HDAC inhibitor, the treatment strategy is more targeted, and is expected to reduce off-target effects and systemic toxicity; the PTN and the extracellular vesicle loaded with PTN can be developed for preparing a medicine for diabetic nephropathy, and have good practicability.

The invention discloses a Chinese and western medicine composition and a preparation method and application thereof, and belongs to the technical field of anti-lung cancer targeted drugs, the traditional Chinese medicine composition and EGFR-TKI cooperate to treat EGFR mutation advanced non-small cell lung cancer, the lifetime of a patient is prolonged, the treatment effective rate is increased, the life quality is improved, and the side effect of the targeted drugs is relieved. Compared with EGFR-TKI single medicine treatment, the traditional Chinese medicine composition is combined with EGFR-TKI, proliferation of HCC827 lung cancer cells is remarkably enhanced and inhibited, cell apoptosis is promoted, cycle division of cells is interfered, the traditional Chinese medicine and western medicine composition provided by the invention has the advantages that by regulating and controlling tumor cell energy metabolism and regulating and controlling expression of metabolism-related proteins LDHA, HK2, GLUT1 and HIF-1alpha, the effect of inhibiting HCC827 lung cancer cells is achieved, and the curative effect of the HCC827 lung cancer cells is improved. Therefore, effective control of the advanced non-small cell lung cancer is realized.

The application discloses an NAD + The application discloses a related nanopharmaceutical brain-targeting delivery system, a preparation method and application thereof, and the delivery system is composed of a carrier shell containing NAD + The related active ingredient is composed of a core of the related active ingredient and a carrier shell of a surface-modified brain-targeting ligand, NAD + The related active ingredient is complexed and coordinated to realize high drug loading and stable encapsulation, and multiple types of brain-targeting ligands are jointly modified to make the delivery system have the ability of transporting across the blood-brain barrier and locating in brain cells. + The application combines the supplement with a GLUT1 / RVG double-ligand brain-targeting strategy to construct a safe, high-drug-loading and high-stability NAD + The related nanopharmaceutical system can improve the NAD(H) content of brain tissues, improve mitochondrial function, reduce oxidative stress and neural inflammation, and reverse or reduce the aging phenotype of astrocytes, and provides a new drug delivery strategy for Parkinson's disease and aging-related neurodegenerative diseases.

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a WZB117 nano preparation and a preparation method thereof. In the treatment of uveal melanoma, there is a lack of effective treatment scheme. The application provides a novel ophthalmic preparation and a preparation method thereof, and utilizes hemoglobin and dopamine to simultaneously carry a glucose transporter 1 (Glut1) inhibitor WZB117 and copper ions. The nano preparation can form a positive feedback cycle through a copper death-induced active oxygen burst and an antioxidant system collapse caused by WZB117 double-sulfur death, so as to accelerate tumor cell death.

The present invention discloses an application of an E3 ubiquitin ligase RBCK1 in the preparation of a drug for treating liver cancer. The present invention has found that high expression of RBCK1 is significantly associated with poor tumor survival and distant invasion. Functional experiments have shown that RBCK1 promotes migration and invasion by enhancing GLUT1-mediated aerobic glycolysis, and RBCK1 activates the WNT / β-catenin / GLUT1 pathway to induce HCC cell migration and aerobic glycolysis dependent on the destruction of the PPARγ / PGC1α complex. RBCK1 promotes PPARγ ubiquitination degradation, and RBCK1 overexpression enhances WNT / β-catenin transcriptional activity, thereby upregulating GLUT1-mediated aerobic glycolysis of HCC cells. Both in vivo and in vitro, RBCK1 plays an important role in the occurrence and progression of liver cancer cells, and based on the high expression results of RBCK1 in liver cancer tissues, a powerful means is provided for potential targeted treatment of liver cancer patients in the future.

The invention belongs to the field of drug delivery system construction, and particularly relates to a target-drug self-adaptive transformation cross-linking self-assembly nano platform as well as a preparation method and application of the target-drug self-adaptive transformation cross-linking self-assembly nano platform. The doxorubicin is creatively taken as a carrier and a targeting ligand for oral delivery of the doxorubicin, so that the specific targeting and treatment effects of a tumor part are realized. The doxorubicin hydrochloride is subjected to stable self-assembly by virtue of disulfide bond crosslinking through a specific crosslinking material, a hydrophilic end sugar ring of the doxorubicin hydrochloride is anchored on the surface of a nanoparticle, and an intestinal epithelial cell barrier and a blood brain barrier are crossed by recognizing SGLT1 and OCTN2 which are highly expressed on a top side membrane of an intestinal epithelial cell, GLUT2 on a substrate side and GLUT1 on the surfaces of brain microvascular endothelial cells and glioma cells. The nanoparticles not only significantly improve the oral bioavailability of adriamycin, but also have an efficient accumulation effect in the brain, further break disulfide bonds and release adriamycin in a high-GSH environment, and achieve a safe and efficient anti-tumor effect.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a WZB117 nano preparation and a preparation method thereof. In the treatment of uveal melanoma, an effective treatment scheme is lacked. According to the novel ophthalmic preparation and the preparation method thereof, hemoglobin and dopamine are used for carrying a glucose transporter 1 (Glut1) inhibitor WZB117 and copper ions at the same time, the nano preparation can form positive feedback circulation through active oxygen outbreak induced by copper death and anti-oxidation system collapse caused by WZB117 disulfide death, and tumor cell death is accelerated.

The present invention belongs to the field of medicinal chemistry and relates to a triazine-thiazolidinone compound and its preparation method and application. The triazine-thiazolidinone compound structural formula is wherein R1 is any one of an alkyl, aryl or heteroaryl group, and R2 is an alkyl or aryl group; its pharmaceutically acceptable salt is an acid salt of the compound, and the acid is any one of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, boric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, benzenesulfonic acid, citric acid, lactic acid, pyruvic acid, tartaric acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, salicylic acid or phenylacetic acid. The triazine-thiazolidinone compound provided by the present invention has a novel structure and has a good inhibitory effect on glucose transporter 1 (GLUT1). In HT29 cells, its inhibitory effect is better than that of the positive control compound BAY-876, and has a good potential for further development as an anti-tumor drug.

This invention provides a screening method for occludin expression-promoting components, using the expression level of GLUT1 in skin tissue as an indicator. [Solution] A screening method for occludin expression-promoting components using the expression level of GLUT1 in skin tissue as an indicator.

IMPROVED GLUT1-BINDING POLYPEPTIDES The present invention relates to a glucose transporter protein type 1 (GLUT1)-binding polypeptide comprising, or consisting of, an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 22 to 26, and variants or fragments thereof, wherein the sequences of said variants or fragments comprise a serine (S) residue at position corresponding to position 95 of SEQ ID NO: 1, 23 and 25, or to position 97 of SEQ ID NO: 22, 24 and 26. The present invention further relates to in vitro and in vivo methods of specifically detecting or / and measuring the level of GLUT1, and to the use of said polypeptides in diagnosis and therapy.

The invention discloses an application of a PKM2 / GLUT1 axis in T2DM cataract, belongs to the technical field of biological medicine, aims to solve the problem that the PKM2 / GLUT1 axis is unclear in action in cataract pathogenesis of a T2DM patient, and explores whether PKM2 / GLUT1 axis imbalance mediates mitochondrial dysfunction to play a role in the cataract of the T2DM patient through culture of a clinical sample and a human LECs cell line cultured in vitro. It is found that PKM2 / GLUT1 axis imbalance can promote occurrence and development of cataract of T2DM patients, and the mechanism may be related to mediated LECs mitochondrial dysfunction and apoptosis. By improving the activity of the PKM2, lens opacity in a high-glucose environment can be slowed down, so that a new strategy is provided for preventing and treating cataract of a T2DM patient.

The invention discloses an application of sgRNA for targeted knockout of a bovine FGFR1 gene in construction of a bovine mammary epithelial cell line. The nucleotide sequence of the sgRNA is as shown in SEQ ID NO: 1. According to the mammary epithelial cell line constructed and obtained by utilizing the sgRNA through a CRISPR / Cas9 technology, the FGFR1 protein expression quantity is remarkably reduced, the activity and proliferation condition of mammary epithelial cells are not remarkably influenced after the FGFR1 gene is knocked out, mRNA expression of proliferation key genes PCNA, Cyclin D1 and Cyclin E1 in the cells is not remarkably changed, and the mammary epithelial cell line can be used for preparing a mammary epithelial cell line. However, expression of milk protein synthesis related genes (such as CSN1S1, CSN2, CSN3 and EFL5), lactose synthesis related genes (GLUT1 and HKII) and milk fat synthesis related genes (SCD-1) is remarkably reduced, and a key tool is provided for deep analysis of a regulation mechanism of FGFR1 in biological behaviors such as mammary epithelial cell proliferation and lactation synthesis.

The present invention relates to the use of the proportion of plasma cells, lymphocytes or blasts expressing GLUT1 among total plasma cells, lymphocytes or blasts in a method for stratifying prognosis of subjects suffering from a hematologic disorder, and in a method for determining whether a subject suffering from a hematologic disorder will achieve or is achieving a response with a modulator of the BCL-2 family proteins. The present invention also relates to a kit for detecting GLUT1, and optionally ASCT2, for implementing one of these methods.