13results about How to "Inhibit phosphorylation" patented technology

The invention provides a cucurbitacine compound as well as a preparation method and application thereof, and belongs to the field of medicinal chemistry. The cucurbitacine compound shown in the formula I is extracted and separated from picria fel-terrae and is a furocoumarin compound, phosphorylation of STAT3 in triple negative breast cancer cells can be inhibited, expression of downstream apoptosis-related proteins PARP and Caspase3 is further affected, apoptosis of the triple negative breast cancer cells is promoted, and the cucurbitacine compound can be used for treating the triple negative breast cancer cells. Therefore, the effect of inhibiting the growth of the triple-negative breast cancer is achieved, and the compound has a wide application prospect in preparation of drugs for preventing and / or treating the triple-negative breast cancer. And the formula I of the # imgabs0 # is shown in the specification.

The invention belongs to the technical field of biological medicine, and particularly relates to application of cynarin as a cGAS-STING signal channel inhibitor in preparation of anti-inflammatory drugs. It is found for the first time that cynarin can inhibit phosphorylation of STING and translocation of STING by influencing the stability of STING spatial conformation, so that channel downstream protein activation is inhibited, nuclear translocation of IRF3 is hindered, expression of a series of interferon-induced related genes such as IFN-beta, CXCL10 and ISG15 is inhibited, finally secretion of IFN-beta can be hindered, cGAS-STING inflammatory response can be inhibited by targeting STING, and the application of cynarin in inhibiting cGAS-STING inflammatory response is achieved. A new thought and a new means are provided for developing an auxiliary treatment method aiming at STING related inflammations.

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a parent structure of a PKM2 agonist and application of the PKM2 agonist, the PKM2 agonist is hypaconitine screened from a monkshood alkaloid part, the chemical formula of the PKM2 agonist is C33H45NO10, and the structural formula of the PKM2 agonist is shown in the description. The hypaconitine has the functions of inhibiting phosphorylation of tumor cell PKM2 protein, inhibiting conversion from tetramer to dimer, enhancing PKM2 activity and inhibiting PKM2 nuclear translocation; the parent structure of the hypaconitine is composed of diterpenoid skeleton atoms, and the parent nucleus of the hypaconitine is C19 diterpenoid alkaloid; according to the invention, a PKM2 activating component in monkshood alkaloid is screened by using computer-aided drug design, and it is reported for the first time that hypaconitine has a PKM2 activating effect; a certain foundation is laid for the research on the anti-tumor mechanism of the radix aconiti carmichaeli, a basis is provided for the clinical application of the anti-tumor of the radix aconiti carmichaeli, and a new parent structure is provided for the research and development of a PKM2 agonist.

The application discloses a method for efficiently separating high-purity conjugated linoleic acid from Tetrastigma hemsleyanum, which takes stems and leaves of Tetrastigma hemsleyanum as raw materials, and sequentially carries out ethanol extraction, ethyl acetate extraction, normal-phase silica gel column chromatography, gel column chromatography and semi-preparative reverse-phase liquid chromatography coupling purification process, so that 10E, 12Z-CLA monomers with chemical purity of greater than or equal to 99% are efficiently prepared. Experiments prove that the compound can significantly inhibit the inflammatory reaction of macrophages induced by lipopolysaccharide, and the mechanism is that the compound down-regulates TLR4 protein expression and inhibits NF-kappa B p65 phosphorylation, so as to block the activation of the TLR4 / NF-kappa B signal pathway. The application realizes high-value utilization of the abandoned resources of Tetrastigma hemsleyanum, and the obtained product can be used as a definite active ingredient for developing anti-inflammatory drugs, functional foods or cosmetics.

The invention relates to the field of medicinal chemistry, in particular to a CDK6 / 9 dual inhibitor and a preparation method and application thereof.The CDK6 / 9 dual inhibitor has CDK6 and CDK9 inhibitory activity at the same time, has an inhibitory effect on abnormal hyperplasia of a psoriasis cell model and inflammatory factor disorder and has good safety and selectivity in a CDK family; the inhibitor can be used as a therapeutic drug for psoriasis dermatitis, psoriatic arthritis and other autoimmune diseases.

The present application relates to the technical field of biology, and particularly discloses a kind of tyrosine iodination modified PP2A protein monoclonal antibody, preparation method and application.The present application is prepared by tyrosine iodination modified PP2A protein antigen peptide, rabbit is immunized to prepare monoclonal antibody, and is selected by phage display technology, expression vector amplification and ELISA screening, finally obtains a strain of monoclonal antibody R004 that can effectively recognize target.The antibody shows good sensitivity and specificity in immunohistochemistry, cell immunofluorescence and protein immunoblotting.The monoclonal antibody screened in the present application can be used in the detection of tyrosine iodination modification of PP2A protein catalytic subunit 307, and provides support for tumor diagnosis, anti-tumor and neurological disease drug research and development.

The application belongs to the technical field of biological medicine, and particularly relates to an interfering peptide for regulating NR4A3 S280 phosphorylation, application thereof and a marker for liver cancer diagnosis. The interfering peptide is a sequence shown in SEQ ID NO. 1. The application proves that the interfering peptide can significantly restore the formation of the condensate of NR4A3, and further inhibit the progression of liver cancer in cell experiments and animal experiments. The targeted regulation of biomolecular condensate formation represents a promising oncology treatment approach, and the application provides a conceptual framework.

The invention provides a topoisomerase I / II double-target inhibitor as well as a preparation method and application thereof, and belongs to the field of medicines. 6-bromoheliotropin is used as a raw material to synthesize the compound with the structural formula shown in the formula I. The compound is a novel topoisomerase I / II double-target inhibitor, can be used for treating small cell lung cancer, advanced metastatic ovarian cancer, advanced breast cancer, colorectal cancer, bladder cancer and other diseases, and has a good application prospect. # imgabs0 #

The invention discloses an application of circRERE-AAV in preparation of a composition for treating colorectal cancer. The nucleotide sequence of circREE in the circRERE-AAV is shown as SEQ ID NO.01. The invention further discloses a preparation method of the circRERE-AAV. The circREE disclosed by the invention is regulated and controlled by EP300 and is low in expression in colorectal cancer; the circREE can adsorb miRNA miR-6837-3p, and after expression of the circREE is reduced, more miR-6837-3p can be released to be combined with MAVS, so that degradation of the MAVS is promoted, and phosphorylation of TBK1, IRF3 and NF kappa B is inhibited; therefore, I-type interferon and proinflammatory cytokines are reduced, and tumor growth is promoted.

The invention provides a CSF1R kinase inhibitor compound or a pharmaceutically acceptable salt thereof and application of the CSF1R kinase inhibitor compound or the pharmaceutically acceptable salt thereof in medicines for treating diseases related to a CSF1R kinase signal transduction pathway or regulating immunity.

The invention relates to a phloroglucinol compound, separation and application of the phloroglucinol compound in preparation of drugs for resisting acute myeloid leukemia, and belongs to the technical field of medicines. The novel compound long-column polycycline A separated from the plant hypericum has good anti-tumor activity, especially has good anti-tumor activity on AML cell lines, and can be used as a lead compound for development of anti-AML drugs. The invention provides an alternative compound for research and development of new drugs for resisting acute myeloid leukemia cells, and has very important significance for development and utilization of natural product resources.

The present invention discloses a polypeptide, a nucleic acid molecule, a cell and their application in breast cancer, and relates to the technical field of breast cancer treatment. The present invention provides a polypeptide targeting cGAS phosphorylation, which can significantly inhibit the phosphorylation of cGAS in triple-negative breast cancer (TNBC), thereby inhibiting the metastasis of cancer, and can be used for the treatment of breast cancer (especially TNBC). In addition, the present invention also provides a nucleic acid molecule, a vector, a cell and a drug encoding the above polypeptide, which has good application prospects.

This invention belongs to the field of pharmaceutical technology and discloses the inhibitory effects and mechanisms of action of sclerotinib on lung cancer cells, cervical cancer cells, and ovarian cancer cells. Compared with the currently available broad-spectrum antitumor drug fluorouracil, sclerotinib exhibits superior antitumor properties. In-depth research revealed that sclerotinib acts on the novel protein STAT3 in cancer treatment, inhibiting STAT3 phosphorylation and preventing phosphonate-modified protein dimers from entering the cell nucleus to initiate transcription. Furthermore, sclerotinib inhibits the downstream anti-apoptotic protein BCL-2 of STAT3, synergistically inhibiting tumor cell proliferation. In this study, based on the half-maximal inhibitory concentration (IC50) results of sclerotinib against lung cancer cells A549, cervical cancer cells HeLa, and ovarian cancer cells A2780, we directly verified the anticancer target of sclerotinib through experiments, elucidated its anticancer mechanism, and provided theoretical and experimental basis for its entry into preclinical and clinical trials.