21 results about "PKM2" patented technology

The present invention relates to a complex comprising a polysaccharide conjugate, an anti-PD-L1 monoclonal antibody, and a PKM2 inhibitor. The complex of the present invention can accumulate and remain in tumor tissue, effectively stimulate dendritic cell maturation, alleviate the inhibitory immune microenvironment, and trigger a specific anti-tumor immune response. It can effectively inhibit the expression of PKM2, thereby inhibiting glycolysis in tumor tissue and providing a more favorable environment for T lymphocytes to infiltrate tumor tissue. The complex of the present invention is expected to enhance the therapeutic effect of RFA on patients with advanced HCC by reprogramming iRFA-induced tumor immunosuppression, and has great potential in improving the prognosis of patients with advanced HCC treated with RFA.

The invention discloses application of eupatolide in preparation of a medicine for preventing and treating inflammatory bowel disease, application of eupatolide in preparation of a medicine for preventing and treating inflammatory bowel disease and application of a medicine preparation containing eupatolide in preparation of a medicine for preventing and treating inflammatory bowel disease, and researches that eupatolide (EPT) can be used for preparing the medicine for preventing and treating inflammatory bowel disease through targeting pyruvate kinase isoenzyme 2 (PKM2, Gene ID: 5135). The inflammatory response, glycolysis metabolism and mitochondrial homeostasis are synergistically regulated and controlled, so that the inhibition effect on the inflammatory bowel disease is exerted. Meanwhile, EPT has the advantages of being low in dosage, feasible in oral administration, free of obvious toxic and side effects and the like, and a solid experimental basis is provided for further developing EPT into candidate drugs for preventing and treating inflammatory bowel diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a PPARalpha agonist combined with an NPC1L1 inhibitor in tumor treatment. Specifically, it is proved for the first time that systemic PKM2 deficiency can cause increase of the total cholesterol level and promote growth of homologous allograft tumors, and the phenomenon is partially attributed to increase of the expression level of intestinal NPC1L1. In addition, in breast cancer cells, PKM2 gene knockout not only weakens the activity of a PPARalpha signal channel, but also improves the expression of NPC1L1. Fenofibrate and Ezetimibe can be used for cooperatively inhibiting proliferation and metastasis of tumor cells in vitro and in vivo, so that the Fenofibrate and Ezetimibe have important clinical significance and social value.

The invention relates to the technical field of biological medicines, in particular to application of tetramer-form pyruvate kinase type 2 (PKM2) in preparation of a medicine for treating obesity. Pyruvate kinase type 2 is a key enzyme in a glycolytic pathway and has two conformations of dimer and tetramer, and the tetramer-form enzyme has high activity. The invention discovers that the PKM2 tetramer stabilizer TEPP-46 can stabilize PKM2 in a high-activity tetramer state and improve obesity-related metabolic disorder induced by high fat diet. The invention discloses a new way for regulating and controlling energy metabolism by stabilizing the form of the PKM2 tetramer, and provides a new medicine application direction for treating obesity and related metabolic diseases.

The invention relates to the technical field of medicines, and particularly discloses an application of artemether in preparation of an esophageal cancer radiotherapy sensitization medicine. The invention provides the application of artemether in preparation of esophageal cancer radiotherapy sensitization drugs for the first time, and researches find that the artemether can reduce glycolytic activity of esophageal cancer cells by down-regulating expression of key proteins and genes HK2, PKM2 and LDHA in a glycolytic pathway so as to enhance esophageal squamous cell carcinoma radiotherapy sensitization. The invasion ability is inhibited, and cell apoptosis is induced, so that the radiotherapy sensitivity of esophageal cancer cells is enhanced. The artemether and radiotherapy combined treatment provided by the invention is expected to provide a promising treatment scheme for ESCC patients, and has great significance in breaking through the bottleneck of esophageal cancer radiotherapy.

The invention relates to a PKM2-based nano glycopeptide activator and application thereof.The nano glycopeptide activator comprises three functional units, namely a PKM2 targeted activation unit R3, a self-assembly unit R2 and a response unit R1, and the chemical structure of the nano glycopeptide activator is shown in the formula (I). After administration, the nano glycopeptide activator can be enriched to a tumor site through targeting of sugar receptor transporter protein or an EPR effect; after entering tumor cells, the polypeptide is subjected to in-situ fibrosis deformation under the hydrolysis action of glycohydrolase, so that specific targeting and retention are realized; the nano-fiber with the PKM2 targeting activation unit can promote conversion of dimer PKM2 into tetramer PKM2, inhibit nucleation of PKM2, and prevent the DNA damage repair process of tumor cells.

Provided for are activators of pyruvate kinase isoform M2 (PKM2), pharmaceutical compositions thereof, and related methods of treating neurologic and neurodegenerative disease as well as well as other PKM2-associated disorders.

Provided is a chiral cannabidiol (CBD) derivative drug, comprising four chiral derivatives, i.e., (7S)-(-)-CIAC001, (7R)-(-)-CIAC001, (7S)-(+)-CIAC001, and (7R)-(+)-CIAC001; and a use of the four chiral derivatives of CBD in the treatment of neuroinflammation and opioid addiction. Also disclosed are anti-neuroinflammation effects and the ability to regulate the activity of pyruvate kinase M2 (PKM2) of CBD analogs.

The invention belongs to the technical field of immunotherapy, and particularly relates to a method for improving the effector function of NK (Natural Killer) cells, which is characterized in that a glycolysis metabolism process is influenced and the generation of lactic acid is reduced by constructing point mutation vectors PKM2-322K-R and PKM2-433K-R of a PKM2 gene so as to inhibit the level of lactic acid modification. The invention also provides a construction method of the NK92MI cell of the PKM2 protein. The construction method comprises the following steps: constructing a vector, extracting plasmids, packaging concentrated viruses and transfecting target cells. According to the present invention, the protein targeting lactylation modification is adopted to modify and block the lactylation modification so as to reverse the function depletion of the NK cell, the PKM2 delactylation is performed through the point mutation so as to partially reverse the NK cell function, and the expression level of the effector molecule of the NK92MI cell is recovered;

A method for treating brain injury in a subject comprises administering a therapeutically effective amount of a PKM2 (pyruvate kinase M2) protein variant. The protein variant is delivered systemically and can reduce tissue damage after ischemic brain tissue reperfusion. The methods specifically involve the use of G415R mutants of PKM2 protein variants. The treatment is suitable for brain injury caused by hemorrhagic stroke and ischemic stroke. The PKM2 protein variants are ideally administered intravenously within one hour of reperfusion to maximize their therapeutic efficacy.

The invention relates to the technical field of biological medicines, and particularly discloses a novel target MFN2 protein, a targeted small-molecule compound salvianolic acid B thereof and application. The technical key points are as follows: the diagnosis and treatment effect of the MFN2 protein as a novel target in rheumatoid arthritis (RA) and the application of the MFN2-targeted small molecular compound salvianolic acid B in preparation of drugs, food or health care products for treating RA. The medicine, food or health care product comprises a medicine which takes MFN2 protein as a target spot and mainly inhibits MFN2 mediated M1 polarization in mononuclear / macrophages. It is found for the first time that MFN2 protein in peripheral blood mononuclear cells of an RA patient participates in M1 polarization of mononuclear / macrophages, and a natural small molecule compound Sal-B can inhibit the MFN2-mediated M1 polarization tendency of the mononuclear / macrophages by inhibiting interaction of the MFN2 protein and PKM2 protein, so that inflammation and bone destruction are relieved, and the effect of treating RA is achieved.

This provides a method for treating patients suffering from diseases caused by organ / tissue fibrosis. [Solution] The method includes administering a PKM2 activator. The PKM2 activator can reduce LOX protein expression and activate PKM2.

A method of treating a patient suffering from disease that is caused by organ / tissue fibrosis includes the administration of a PKM2 activator. The PKM2 activator can reduce LOX protein expression and activate PKM2.

The invention discloses an application of LNK as a biomarker in cerebral arterial thrombosis diseases. The invention reveals that the lymphocyte adapter protein (LNK) has a fluctuation decreasing trend after cerebral arterial thrombosis for the first time, and the expression deletion of the lymphocyte adapter protein promotes the polarization of microglial cells to M1 type, increases the secretion of proinflammatory factors such as TNF-alpha and IL-1beta, and aggravates nerve injury. Cerebral infarction volume and neurological dysfunction can be remarkably improved through LNK overexpression (animal model verification). In mechanism, LNK regulates the phenotype of microglial cells through glycometabolism reprogramming, and specifically inhibits the expression of pyruvate kinase PKM2 so as to alleviate inflammatory response. On the basis, the LNK can be used as a dynamic biomarker for early diagnosis of cerebral arterial thrombosis, two new treatment strategies of an LNK activator and a PKM2 inhibitor are provided, the time window limitation of existing thrombolysis treatment is broken through, and a brand-new target is provided for neural immune metabolism intervention.

Provided are a PKM2-based nanoglycopeptide activator and a use thereof. The nanoglycopeptide activator comprises three functional units, namely a PKM2-targeted activation unit R3, a self-assembly unit R2, and a response unit R1. The chemical structure of the nanoglycopeptide activator is as shown in formula (I). Upon administration, the nanoglycopeptide activator can be enriched at a tumor site by means of glucose receptor transporter-mediated targeting or the EPR effect; after entering tumor cells, the nanoglycopeptide activator undergoes in-situ fibrotic deformation under the hydrolysis action of glycosidase, thereby achieving specific targeting and retention; and nanofibers having the PKM2-targeted activation unit promote the conversion of dimeric PKM2 into tetrameric PKM2, inhibit the nuclear translocation of PKM2 , and block the DNA damage repair process in the tumor cells.

The invention belongs to the technical field of biological medicine, and particularly relates to application of a short peptide entrapped by lung-targeted liposome and used for blocking combination of PKM2-FOXO3A in preparation of a medicine for treating stroke-related lung injury, the amino acid sequence of the short peptide is shown as SEQ ID NO.1, the SEQ ID NO.1 RKGEDREGKR and Pe (at) P-Lipo can be used for remarkably relieving MCAO mouse lung tissue pathological injury, and can be used for preparing a medicine for treating stroke-related lung injury. According to the present invention, with the application of the cerebral ischemia injury in the lung, the total reactive oxygen species (ROS) level in the lung tissue and the mitochondrial ROS level, the reduction of the ATP content can be reversed, the level of the lung tissue inflammation-related protein can be reduced, and the enrichment of PKM2, FOXO3A and TXNIP in the mitochondria can be reduced so as to alleviate the lung tissue oxidative stress and the mitochondrial injury caused by the cerebral ischemia injury, and provide the lung protection effect;

Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.

The present disclosure relates to the use of pyruvate kinase M2 in the diagnosis and prognosis of heart failure, belonging to the field of in vitro diagnostic technology. After excluding patients with malignant tumors, the present disclosure found that the level of pyruvate kinase M2 in the plasma of patients with heart failure was higher than that of normal patients without heart failure. In particular, the level in patients with left ventricular failure and total heart failure was significantly higher than that of normal patients without heart failure. The level in the plasma of patients with acute heart failure was also significantly higher than that of normal patients without heart failure. As a marker for heart failure, PKM2 has high accuracy in diagnosing heart failure and assessing its prognosis, providing a new and improved option for the prediction, diagnosis, auxiliary diagnosis, and prognosis of heart failure.

The application belongs to the technical field of immunotherapy, and particularly relates to a method for improving the effect function of NK cells, wherein point mutation vectors PKM2-322K-R and PKM2-433K-R of a PKM2 gene are constructed, the glycolysis metabolic process is affected, the generation of lactic acid is reduced, and the lactic acidification modification level is inhibited. The application further provides a construction method of NK92MI cells of a PKM2 protein, and the steps include constructing a vector, extracting a plasmid, packaging and concentrating viruses, and transfecting target cells. The application targets lactic acidification modification, a protein modification, blocks lactic acidification modification, reverses the functional exhaustion of NK cells, makes PKM2 de-lactic acidification through point mutation, can partially reverse the function of NK cells, and restores the expression level of effect molecules of NK92MI cells.

This invention provides the application of agents that inhibit NNMT binding to FGFR1 in the prevention and treatment of tumors. Through mutation analysis and interactomics analysis, it reveals a previously unknown, non-enzyme-dependent role of NNMT in promoting aerobic glycolysis in breast cancer. It discovers that NNMT binds to FGFR1 and acts as a scaffold protein, promoting phosphorylation of PKM2 and LDHA at Y105 and Y10 sites, respectively. By positioning the FGFR1 binding interface to the 140-154 amino acid region of NNMT, this invention designs a competitive cell-penetrating peptide, NNMT-15, which can disrupt the NNMT-FGFR1 interaction, reduce the phosphorylation levels of PKM2 and LDHA, inhibit glycolysis, and suppress proliferation in NNMT-high-expressing cancer cells and cancer-associated fibroblasts. These findings reveal NNMT as a dual-function metabolic regulator and establish the NNMT-FGFR1 scaffolding effect as a targeted therapeutic axis in glycolysis-dependent tumors.

The present invention relates to prevention of congenital deformations. The invention further relates to cancer inhibition and prevention. The invention further relates to methods and compositions to modulate, antagonize, or agonize disparate signaling pathways that may converge to regulate patterning events and gene expression during prenatal development, postnatal development, and during development in the adult organism. The invention also relates to activators or deactivators of pyruvate kinase M2 (PKM2) for the treatment, prevention, or amelioration of diseases related to PKM2 function.