9 results about "Mdm2 Protein" patented technology

The invention belongs to the technical field of biological medicines, and relates to a protein degradation system based on polyamide-amine dendrimers as well as a preparation method and application of the protein degradation system. The protein degradation system is of a nano-particle structure, and the nano-particle structure comprises silicon dioxide nano-particles and a polyamide-amine type dendritic polymer layer coating the surfaces of the silicon dioxide nano-particles. An MDM2 protein ligand, a GLUT1 protein ligand and an E3 ubiquitin enzyme ligand are connected to the polyamide-amine dendritic polymer layer through chemical bonds. The protein degradation system provided by the invention can be used for synergistically degrading the MDM2 protein and the GLUT1 protein. The synergistic degradation strategy not only can effectively inhibit proliferation and energy metabolism of tumor cells, but also can significantly enhance the stability of the p53 protein. By recovering the normal function of the p53 protein, the growth of tumor cells is further inhibited, and a new strategy is provided for tumor treatment.

The invention discloses beta-carboline alkaloid and application of the beta-carboline alkaloid in preparation of antitumor drugs. The beta-carboline alkaloid disclosed by the invention can be used as an MDM2 protein inhibitor, and can effectively inhibit the proliferation of colorectal cancer and induce cell apoptosis.

The present disclosure provides compounds represented by Formula I-A:A1-L1-B1  I-Aand the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A1, B1, and L1 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a condition or disorder responsive to degradation of MDM2 protein such as cancer.

The invention relates to an MDM2 protein targeted fluorescent probe, an MDM2 protein targeted degradation fluorescent probe and a preparation method and application thereof.The MDM2 protein targeted fluorescent probe comprises fluorescent molecules and multifunctional polypeptide which are connected with each other, and the multifunctional polypeptide comprises alkynyl, a fluorine-substituted aryl fluorosulfate structure and MDM2 protein targeted peptide; and reacting the fluorescent molecule with alkynyl of the multifunctional polypeptide to obtain the MDM2 protein targeting fluorescent probe. According to the present invention, the fluorine-substituted aryl fluorine sulfate structure on the multifunctional polypeptide can be subjected to specific covalent binding with the MDM2 protein, and the fluorescent molecule and the MDM2 protein interact so as to allow the fluorescent probe to release the fluorescent signal, such that the detection of the intracellular MDM2 protein is achieved. Compared with the MDM2 protein targeted fluorescent probe, the MDM2 protein targeted degradation fluorescent probe has the advantages that the E3 ubiquitin ligase recruitment peptide is added, so that the degradation of MDM2 protein in cells can be induced, and the degradation process can be monitored in real time.

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 application belongs to the technical field of biological medicine, and relates to a protein degradation system based on a polyamide-amine dendritic polymer, and a preparation method and application thereof. The protein degradation system is in a nanoparticle structure, the nanoparticle structure comprises a silica nanoparticle and a polyamide-amine dendritic polymer layer coated on the surface of the silica nanoparticle, and MDM2 protein ligands, GLUT1 protein ligands and E3 ubiquitin enzyme ligands are connected on the polyamide-amine dendritic polymer layer through chemical bonds. The protein degradation system provided by the application can synergistically degrade MDM2 protein and GLUT1 protein. This synergistic degradation strategy can not only effectively inhibit the proliferation and energy metabolism of tumor cells, but also significantly enhance the stability of p53 protein. By restoring the normal function of p53 protein, the growth of tumor cells is further inhibited, thereby providing a new strategy for tumor treatment.

The present invention provides a dispiropyrrolidine derivative represented by the following formula (1), which has various substituents, inhibits interaction between Mdm2 protein and p53 protein and exhibits anti-tumor activity, wherein R1, R2, R3, ring A, and ring B in formula (1) respectively have the same meanings as defined in the specification.

The present application provides protein degradation targeting chimeras, methods of making, pharmaceutical compositions, and uses thereof. In particular, the protein degradation targeting chimeras comprise the structure: MDM2 target protein inhibitor-C(O)NH-L 2 -Y 1 -B 1 wherein the groups are as defined in the specification. The compounds are useful for treating conditions or disorders (e.g., cancer) that are responsive to degradation of MDM2 protein.

The invention discloses a marker for prognosis layering of mucus fibrosarcoma and application of the marker, and belongs to the technical field of biological medicine. The MDM2 protein or the number 12 chromosome polysome has obvious correlation with the prognostic stratification of the mucus fibrosarcoma, the MDM2 protein or the number 12 chromosome polysome is used as the marker for the prognostic stratification of the mucus fibrosarcoma, and a reagent for preparing and detecting the two markers can be applied to judging the prognostic stratification of the mucus fibrosarcoma. The marker disclosed by the invention is abnormal in protein level or specific chromosome structure, and compared with a gene-level marker, the marker disclosed by the invention is easier to carry out standardized detection and interpretation through conventional technologies such as immunohistochemistry and the like, and is suitable for developing related prognosis detection reagents.