40 results about "Phosphorylation Inhibition" patented technology

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

The invention discloses annexin A2 (ANXA2) and application of an inhibitor thereof in diagnosis, treatment and / or prevention of pulmonary arterial hypertension. In particular discloses application of an ANXA2 inhibitor (including siRNA for silencing an ANXA2 gene, an ANXA2 antibody and a phosphorylation inhibitor) in preparation of a product for preventing and / or treating pulmonary arterial hypertension. Experiments prove that the ANXA2 inhibitor can significantly inhibit proliferation and migration of pulmonary artery smooth muscle cells, and significantly improve pulmonary arterial hypertension, pulmonary artery vascular remodeling and right ventricular hypertrophy. The ANXA2 or the Thr208 phosphorylation site of the ANXA2 protein can be used for diagnosis or auxiliary diagnosis of pulmonary arterial hypertension, or used for screening drugs for pulmonary arterial hypertension and developing new diagnosis and treatment methods and drugs. The therapeutic target and the ANXA2 inhibitor developed by the invention have wide clinical application value in the fields of diagnosis, prevention and treatment of pulmonary arterial hypertension.

The invention relates to the technical field of biological medicines, in particular to an iRGD targeted and anti-fibrosis small molecule dual-modified exosome as well as a construction method and application thereof. The exosome utilizes the specific binding penetration enhancement effect of iRGD (the amino acid sequence is CRGDKGPDC) and a fibroblast high-expression integrin receptor, so that the enrichment efficiency of the exosome at a focus part is improved; the anti-fibrosis micromolecule Let-7a-5p can inhibit a TGF-beta signal channel by blocking Smad2 / 3 phosphorylation, and the anti-fibrosis micromolecule Let-7a-5p and the anti-fibrosis microRNA carried by the exosome generate a synergistic anti-fibrosis effect; the exosome phospholipid bilayer can also protect Let-7a-5p from enzymolysis and prolong the half-life period, and iRGD modification can reduce the non-targeted uptake rate. An animal model verifies that the double-modified exosome has a good skin fibrosis resisting effect, and side effects such as liver and kidney function damage are not found. The invention provides an effective and safe treatment scheme for resisting skin fibrosis.

The invention relates to the technical field of targeted intervention of chordoma, in particular to application of a medicine to treatment of chordoma of different molecular types. The invention provides application of anlotinib, an oxidative phosphorylation inhibitor and desumab in preparation of products for preventing and / or treating chordoma. The chordoma comprises interstitial epithelial transformed chordoma, mesenchymal derived chordoma and bone microenvironment dominant chordoma. The invention also provides a pharmaceutical composition, which comprises an effective dose of anlotinib, and / or an oxidative phosphorylation inhibitor, and / or desumab. Under the condition that current treatment selection is limited, proliferation, clone formation and tumor growth of tumor cells can be remarkably inhibited by applying the medicine to specific molecular subtype chordoma, and compared with existing treatment medicine, the medicine has a better treatment effect, has good safety and shows potential clinical application value.

The invention relates to application of a UHRF1 inhibitor in preparation of a medicine for treating tissue fibrosis after spinal cord injury, and belongs to the technical field of biological medicine. The invention proves that the expression of UHRF1 can be increased due to spinal cord injury; compared with mice of a false operation group, the mice of which the UHRF1 is specifically knocked down in the fibroblasts have the advantages that fibrosis caused by spinal cord injury is obviously reduced, nerve regeneration is promoted, and the motor function is obviously improved. In the aspect of mechanism, the knock-down of UHRF1 leads to the reduction of the number of proteins combined on a PPM1A gene promoter, the weakening of the transcription inhibition effect and the promotion of the expression of the PPM1A gene, while the PPM1A can inhibit the phosphorylation of Smad2 / 3 and inhibit the conduction of a TGF-beta1 / Smads pathway, thereby inhibiting tissue fibrosis.

The present invention relates to nuclear mitotic apparatus (NuMA) protein serine 395 (S395) phosphorylation inhibitor for use in preventing and / or treating cancer in a subject. The invention also relates to a pharmaceutical composition comprising a NuMA S395 phosphorylation inhibitor. Furthermore, the invention provides a method of screening for a candidate compound for preventing and / or treating cancer, and a method of detecting a dormant cancer cell in a subject. Corresponding methods of treating and / or preventing cancer are also provided.

The invention belongs to the technical field of biological medicine, and relates to pharmaceutical application of an oxidative phosphorylation inhibitor, in particular to application of the oxidative phosphorylation inhibitor in preparation of an immunomodulatory drug, and the immunomodulatory drug has the advantages that the function damage of newborn myeloid-derived suppressor cells caused by antagonism BCG (bacillus calmette guerin) vaccination is inhibited, and the immunomodulatory effect is improved. The compound is used for preventing or treating neonatal immune-related diseases caused by bacillus calmette guerin vaccine inoculation. The invention finds that the BCG can cause damage to the immunosuppression function of the MDSC of the suckling mouse through up-regulation oxidative phosphorylation, and the negative effect caused by inoculation of the BCG can be reversed by using the OXPHOS inhibitor, so that the immunosuppression function of the MDSC of the suckling mouse is successfully recovered in an in-vivo and in-vitro model, and the immune-related adverse reaction caused by inoculation of the BCG is expected to be improved.

This invention discloses the application and method of a STAT1-targeting inhibitor in the treatment of immune thrombocytopenic purpura (ITP). It employs ivermectin, a STAT1 nuclear translocation inhibitor, and fludarabine, a STAT1 activation inhibitor. By injecting either the activation inhibitor or the nuclear translocation inhibitor, the platelet count in a mouse model of ITP is increased. Fludarabine, a fluorinated nucleotide analog of vidarabine, is non-radioactive and a small-molecule phosphorylation inhibitor. Ivermectin is a small-molecule inhibitor of nuclear translocation mediated by α / β1 introgression protein. Both have high bioavailability and are widely used to treat various hematological diseases with good safety profiles. Their application in treating ITP is safe, effective, and shows high compliance.

The application discloses application of a compound combination in preparation of a drug for treating breast cancer, and the compound combination comprises an exportin XPO1 inhibitor and a CDK4 / 6 inhibitor. The application discloses a new drug administration mode of KPT-330 (selinexor) and a CDK4 / 6 inhibitor in treatment of breast cancer, and the medical name of KPT-330 is selinexor, which is a specific small molecule inhibitor of nuclear export protein 1 (XPO1). The CDK4 / 6 inhibitor is a kind of small molecule compound structural formula, which directly inhibits the formation of a CDK4 / 6-Cyclin D complex, reduces the phosphorylation of RB1, inhibits the release of an E2F family, and plays a role in blocking cells in the G1 phase. The application first proposes the concept of combination of selinexor and the CDK4 / 6 inhibitor in treatment of breast cancer, and is helpful to provide a suitable mode for treating breast cancer patients in the clinic.

The present invention provides a method for screening for a telomerase reverse transcriptase (TERT) phosphorylation inhibitor using TERT or a fragment thereof, and a TERT kinase.

The disclosure provides a hybrid membrane camouflaged nanomedicine loaded with oxidative phosphorylation inhibitor and preparation method thereof. The nanomedicine comprises an inner core and an outer shell coated on the periphery of the inner core. The inner core is a ROS-responsive drug-loaded nanoparticle, and the drug loaded by the ROS-responsive nanocarrier is an oxidative phosphorylation inhibitor. The outer shell is a hybrid membrane of mitochondrial membrane and cancer cell membrane. The nanomedicines can cross the BBB and reach tumor sites by the homologous targeting of cancer cell membrane, and then they can homologously target and enter mitochondria by the mitochondrial membrane. Subsequently, under the high-level ROS environment of the mitochondria, the ROS responsive drug-loaded nanoparticle releases the oxidative phosphorylation inhibitor due to the swell and degradation of the inner core, so that the safe and efficient targeted GBM therapy is achieved.

The invention discloses an application of a polyphyllin monomer drug in cancer treatment. The polyphyllin monomer drug comprises at least one of polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII. The polyphyllin monomer drug inhibits proliferation, migration and angiogenesis of cancer cells and inhibits up-regulation of EGFR (epidermal growth factor receptor) by regulating phosphorylation of FGFR2 and a downstream signal channel thereof, and a new application scheme is provided for cancer treatment.

The invention discloses a nano blocker for hyaluronic acid energy metabolism of a targeted CD44 receptor as well as a preparation method and application of the nano blocker. The nano blocker is a nano preparation obtained by modifying a polylactic acid-glycolic acid copolymer (PLGA) with hyaluronic acid (HA) and then coating the PLGA with nebivolol hydrochloride and 3-bromopyruvic acid, and the nano preparation is marked as NBP-coated PLGA-HA. According to the CD44 receptor targeted hyaluronic acid energy metabolism nano blocking agent disclosed by the invention, bidirectional blocking of basic respiration of tumor cells is realized by using a loaded mitochondrial oxidative phosphorylation (OXPHOS) inhibitor nebivolol hydrochloride and a glycolysis inhibitor 3-bromopyruvic acid; meanwhile, effector immune cells are synergistically enhanced to maintain systemic anti-tumor immunity, high efficiency and safety are shown in in-vitro and in-vivo experiments, and concept paradigm transformation is provided for nano-drug mediated tumor treatment based on energy metabolism.

To provide a novel prophylactic or therapeutic agent for coronavirus infection, the agent containing a substance that has not been known for its therapeutic effect on coronavirus infection as an active ingredient.SOLUTION: The present invention provides a prophylactic or therapeutic agent for coronavirus infection, the agent containing stanniocalcin 1 (STC1) as an active ingredient.SELECTED DRAWING: None

The present invention relates to nuclear mitotic apparatus (NuMA) protein serine 395 (S395) phosphorylation inhibitor for use in preventing and / or treating cancer in a subject. The invention also relates to a pharmaceutical composition comprising a NuMA S395 phosphorylation inhibitor. Furthermore, the invention provides a method of screening for a candidate compound for preventing and / or treating cancer, and a method of detecting a dormant cancer cell in a subject. Corresponding methods of treating and / or preventing cancer are also provided.

The present invention discloses a tumor energy depletion nanoassembly and its preparation method and application, which belongs to the technical field of new excipients and new dosage forms for combined treatment of pharmaceutical preparations. The tumor energy depletion nanoassembly is co-assembled by a mitochondrial oxidative phosphorylation inhibitor and a glycolysis inhibitor through intermolecular forces, and modified with a PEG modifier; the molar ratio of the mitochondrial oxidative phosphorylation inhibitor and the glycolysis inhibitor is 10:1 to 1:10, and the mass ratio of the sum of the mitochondrial oxidative phosphorylation inhibitor and the glycolysis inhibitor to the PEG modifier is 10:90 to 90:10. The tumor energy depletion nanoassembly of the present invention has a high drug loading capacity, good stability, and low toxic and side effects, providing a new strategy for the assembly of homologous synergistic drug nanoparticles, and providing an effective nano-platform for the development of carrier-free hybrid nanoassemblies and energy depletion-driven combined tumor treatment.

The invention discloses clinical application of a metabolic immune and Dai medicine composition in treatment of cancer, the composition comprises: a composition for regulating and controlling tumor cell metabolism, including 2-deoxy-D-glucose, a glycolysis inhibitor, an oxidative phosphorylation inhibitor, a pyruvate dehydrogenase kinase inhibitor, a polyphenol compound and green tea polyphenol; at least one immunomodulator; at least one chemotherapeutic agent; the clinical application of the metabolic immune combined Dai medicine for treating the cancer is realized through action mechanisms in multiple aspects, including influence on the metabolic activity of tumor cells, enhancement of the effect of an immune system, enhancement of the effect of a chemotherapy medicine and leveling of four towers and five components, so that toxin is eliminated, qi and blood are straightened out, resistance is enhanced, and the clinical application of the metabolic immune combined Dai medicine for treating the cancer is realized. The functions of four towers and five components are balanced and coordinated, so that the aim of treating cancers is fulfilled.

The present invention relates to a phlebiarubrone derivative compound represented by structural formula 1. Therefore, the present invention prevents, alleviates or treats inflammatory diseases including atopic dermatitis through inhibition of IgE and IL-4 expression, inhibition of STAT6 phosphorylation, inhibition of degranulation of mast cells, and the like.

The present invention relates to the field of biomedicine and provides the use of a STAT3 dual-phosphorylation inhibitor in the preparation of a drug for preventing or treating triple-negative breast cancer. The STAT3 dual-phosphorylation inhibitor comprises pulsatilla saponin E2 and / or a pharmaceutically acceptable salt thereof. As a STAT3 dual-phosphorylation inhibitor, pulsatilla saponin E2 can effectively inhibit the growth and migration of triple-negative breast cancer cells. Its application in the treatment of triple-negative breast cancer has the advantages of good efficacy and minimal toxic side effects.

An inhibitor of p53 activation for use in haematopoietic stem and / or progenitor cell gene therapy, preferably wherein the inhibitor is an inhibitor of p53 phosphorylation, more preferably an inhibitor of p53 Serine 15 phosphorylation.

The invention provides a method for improving the sensitivity of an esophageal squamous carcinoma (ESCC) patient to neoadjuvant chemoradiotherapy. Specifically, by reducing the levels of CEBPB, AREG and / or EREG proteins, mitochondrial oxidative phosphorylation (OXPHOS) is inhibited, TCA circulation is inhibited, and / or ERBB signal pathways are inhibited, so that the sensitivity of ESCC patients to neoadjuvant radiotherapy and chemotherapy is improved. In addition, the invention also provides a method for predicting the sensitivity of an ESCC patient to neoadjuvant chemoradiotherapy, and a biomarker for predicting the sensitivity of the ESCC patient.

The invention discloses liver-soothing and depression-relieving type medicinal and edible weight-reducing tea based on AMPK / SREBP-1c pathway regulation and control and a preparation method of the weight-reducing tea. A targeted extraction technology is introduced and comprises the steps of step-by-step extraction, embedding purification, liquid phase preparation and the like, key components, such as hawthorn flavone, nuciferine and the like, acting on an SREBP-1c pathway are accurately extracted, the key components and medicinal and edible components such as ginseng, poria cocos and the like in a formula have a synergistic effect, AMPK phosphorylation is effectively activated, SREBP-1c nuclear translocation is inhibited, and the SREBP-1c protein is prepared. Deeper lipid metabolism regulation and control and liver-intestinal axis balance are realized. Cell and animal experiments show that the tea can significantly reduce accumulation of triglyceride and has no side effects of drugs.

In one embodiment, a problem to be solved by the present invention is to provide a new agent the agent being for at least one selected from the group consisting of promoting breast milk secretion, enhancing breast milk secretion function, improving inhibition of breast milk secretion function, and inhibiting mammary gland involution, said agent comprising, as an active ingredient, a substance that has not heretofore been known to have a breast milk secretion promoting effect. The present invention provides an agent for at least one selected from the group consisting of promoting breast milk secretion, enhancing breast milk secretion function, improving inhibition of breast milk secretion function, and inhibiting mammary gland involution, said agent containing a starting material derived from at least one selected from the group consisting of oranges, aloe, carrots, American ginseng, figs, almonds, hyuganatsu, laurel, apples, soybeans, chrysanthemums, wheatgrass, pepper, ginger, ebi-imo, Japanese yams, kuugaimo, Nikko maple, poppies, and radishes.

The application belongs to the technical field of biological medicine, and particularly relates to the use of SH2 domain-containing protein tyrosine phosphatase 1 (SHP1) in the preparation of a drug for treating chronic pain, in particular to the use of SHP1 in the preparation of a drug for treating chronic pain by regulating the morphology of spinal cord astrocytes, the integrity of the blood-spinal cord barrier and the STAT1-CXCL10-CXCR3 neuroimmune signal axis, and a chronic pain treatment strategy based on the signal axis. The application first discloses that SHP1 in spinal cord astrocytes directly dephosphorylates STAT1, inhibits the transcription of CXCL10 and the subsequent infiltration of T lymphocytes into the spinal cord, and discloses the core analgesic mechanism, thereby establishing SHP1 as a new target for treating chronic pain, and opening up a new way for the precise treatment of clinical chronic pain, especially neuropathic pain.

The present invention relates to the use of an inhibitor of UHRF1 in the preparation of a medicament for treating tissue fibrosis after spinal cord injury, belonging to the technical field of biomedicine. The present invention has confirmed that spinal cord injury can lead to an increase in the expression of UHRF1; compared with the mice in the sham operation group, the mice with specific knockdown of UHRF1 in fibroblasts significantly reduced the fibrosis caused by spinal cord injury and promoted nerve regeneration, and the motor function was significantly improved. In terms of mechanism, the knockdown of UHRF1 led to a decrease in the number of its proteins bound to the promoter of the PPM1A gene, resulting in a weakened transcriptional inhibitory effect, promoting the expression of the PPM1A gene, and PPM1A can inhibit the phosphorylation of Smad2 / 3 and inhibit the conduction of the TGF-β1 / Smads pathway, thereby inhibiting tissue fibrosis.

The invention relates to an application of STAT3 or a phosphorylation inhibitor thereof in prevention or treatment of silent corticotropin adenoma, and particularly provides an application of STAT3 or a protein phosphorylation inhibitor thereof in prevention and / or treatment of silent corticotropin adenoma. According to the invention, it is found for the first time that a signal transduction and transcriptional activation factor 3 (Signal Transduction and Transcriptional Activator of Of Transcriptional Activator 3, STAT3) and a phosphorylation site of the STAT3 have specific enrichment in silent corticotropin adenoma, and the application of the STAT3 to the silent corticotropin adenoma has the advantages that the specificity of the silent corticotropin adenoma and the phosphorylation site of the silent corticotropin adenoma is improved;

Provided herein are compositions and methods for treating or preventing metabolic disorders and cancer. In particular, provided herein are compositions, methods, and uses of inhibitors of phosphorylation of AMPKalpha1 at Serine496 and AMPKalpha2 at S491 for improving metabolic function and treating and preventing metabolic diseases (e.g., diabetes and obesity) and cancer (e.g., hepatocellular carcinoma and breast cancer).

The invention provides application of a preparation for regulating ULK1 phosphorylation level in preparation of a product for regulating autophagic flow of immune cells, and belongs to the technical field of biological medicines. In particular to application of a preparation for regulating the phosphorylation level of ULK1 in preparation of a product for inhibiting autophagic flow of immune cells, and the preparation is an STING agonist. The invention finds that STING can regulate and control the phosphorylation state of ULK1 in the autophagy process through direct interaction with ULK1, and can influence the proceeding of autophagy flow, so that through protein-protein interaction, STING agonist inhibits ULK1 activation by directly combining with ULK1 and inducing phosphorylation of Ser757 site of ULK1, and further inhibits a classical ULK1 mediated autophagy pathway.

The invention discloses application of a CCNB1 phosphorylation inhibition tool in preparation of a medicine for preventing and / or treating triple negative breast cancer, and particularly relates to application of a CCNB1 protein S128 site phosphorylation inhibitor in preparation of a medicine for preventing and / or treating triple negative breast cancer. The phosphorylation inhibitor refers to a tool or means used in the process of blocking or weakening protein phosphorylation, particularly a gene editing system, and the 128 serine Ser coded by a CCNB1 gene is mutated into alanine Ala which is recorded as S128A in a target cell. Compared with a traditional small molecule drug, the gene editing tool accurately intervenes phosphorylation modification at the gene level, has the advantages of being clear in mechanism, high in targeting performance, high in safety and the like, is suitable for basic research and potential clinical transformation of TNBC targeted therapy, and has a good application prospect.

The present application relates to the technical field of medicine, and particularly relates to application of ganoderma triterpene in preparation of medicine for treating cervical cancer. Ganoderma triterpene (Ganodecalone A, referred to as GDA) can inhibit migration, proliferation and clonogenic capacity of cervical cancer cells; GDA can arrest the cell cycle of cervical cancer cells in G0 / G1 phase, and with the increase of the concentration of GDA, the proportion of cells in G0 / G1 phase is significantly increased; GDA can promote apoptosis of cervical cancer cells, and with the increase of the concentration of GDA, the proportion of late apoptotic cells is significantly increased; GDA can promote apoptosis of cervical cancer cells by reducing the phosphorylation level of Akt in the cervical cancer cells. GDA and Akt phosphorylation agonist SC79 are mutually antagonistic, and when GDA is combined with Akt phosphorylation inhibitor MK-2206, the apoptosis of two strains of cervical cancer cells is promoted. GDA can induce apoptosis of cells by inhibiting phosphorylation of Akt, up-regulating pro-apoptotic protein Bad and down-regulating anti-apoptotic protein Bcl-2, and thus the anti-tumor effect is exerted.