21 results about "P53 proteins" patented technology

The present invention discloses a small molecule compound having a substituted phenylspiro[indoline-3,3'-pyrrolidine] structure, the structure of which is shown in General Formula I, and the definitions of each substituent as described in the specification and claims. The compound of the present invention can inhibit the protein-protein interactions of MDM2-p53 and MDMX-p53 proteins. As a small molecule inhibitor of the protein-protein interactions of MDM2-p53 and MDMX-p53 proteins, it is used in the preparation of a drug for preventing and / or treating diseases related to MDM2 and MDMX, particularly tumors.

The invention discloses a probe BBM for anchoring OPA1 protein and application of the probe BBM, and belongs to the technical field of biological analysis. Based on the characteristic that the OPA1 protein is rich in hydrophobic amino acid residues and polar amino acids, the probe BBM capable of generating multiple interaction forces with the OPA1 protein is designed by reasonably introducing hydrophobic groups and polar groups. Theoretical calculation and experimental results (including OPA1 knock-down and overexpression) show that the probe realizes efficient enrichment in a mitochondrial inner membrane region. By using the unique probe, the hydrogen peroxide induced mitochondrial inner membrane viscosity change is systematically researched, and the myocardial cell oxidative damage is further confirmed to be realized by a p53 protein mediated apoptosis pathway. The method provides a reliable means for accurately evaluating the oxidative stress of the mitochondrial inner membrane, and has important promotion significance for the development of the cardiovascular research field.

A method of obtaining cell derived vesicles comprising an active wild-type p53 is disclosed. The method comprising: (i) isolating cell derived vesicles from a biological sample comprising cells; and (ii) treating the cell derived vesicles with a DNA damaging agent, or the method comprising: (i) treating cells with a DNA damaging agent; and (ii) isolating cell derived vesicles from a biological sample comprising the cells. A proteinaceous preparation comprising cell derived vesicles and a pharmaceutical composition comprising the proteinaceous preparation are also disclosed. Methods of treating a disease, disorder or condition associated with a mutant or a nonfunctional p53 protein and methods of inducing apoptosis of a target cell comprising a mutant or a nonfunctional p53 protein are also disclosed.

Disclosed herein are heterobifunctional compounds that include a moiety that binds to the Y220C mutant of the p53 protein, a moiety that binds to the effector protein BRD4, and a linker. Also disclosed herein are pharmaceutical compositions comprising the compounds, and methods of using the compounds, e.g., to treat proliferative diseases such as cancers.

The application discloses application of sulforaphane in preparation of an antienterovirus drug and belongs to the technical field of medicines, wherein the sulforaphane can inhibit the expression of viral proteins, inhibit viral genome replication and inhibit the production of virus particles to achieve the purpose of resisting enteroviruses; specifically, the sulforaphane can inhibit the replication of enteroviruses by up-regulating the content of p53 proteins. In addition, the sulforaphane can also be used for reducing the cell morphological damage caused by enteroviruses.

The invention discloses a compound for targeted enhancement of a transcription function of p53 protein and application of the compound. The compound TETACs not only can stabilize a p53 Y220C mutant protein, but also can actively recruit a transcription co-activator to a p53 target gene promoter region and specifically enhance the transcription function of p53, so that the cycle arrest and apoptosis of tumor cells are intensively induced, the tumor growth is effectively inhibited, and the compound TETACs has inhibitory activity on various tumor cells; in addition, as a heterobifunctional molecule, the TETACs play a role in a catalytic and substoichiometric manner, and have a more lasting curative effect and a wider therapeutic window.

The invention belongs to the technical field of gene editing, and particularly relates to a construction method of a transgenic mouse with a tissue-specific precancerous marker. A fertilized ovum is constructed through a gene editing technology, a mutant p53 protein and a fluorescent protein are fused, a loxp-Stop-loxp sequence is added in front of a promoter of a mutant p53 sequence, the fertilized ovum is transplanted into a female mouse, the obtained progeny is an LPL transgenic mouse, and expression inhibition of the mutant p53 protein and the fluorescent protein is achieved; the LPL transgenic mouse is mated with a Cre tool mouse to obtain a transgenic mouse of which the offspring is a tissue-specific precancerous marker, the transgenic mouse expresses mutant p53 protein and fluorescent protein at a specific tissue, early tumor focus development is monitored and traced through a living body fluorescence imaging system, and the LPL transgenic mouse has extremely high application and research values.

Recently, aptamers have been considered in cancer diagnosis and treatment applications by binding to various bioreceptor molecules. Given that the p53 protein is responsible for approximately 50% of cancers, its identification is promising, but so far, no aptamer DNA sequence has been designed for the p53 protein and aptamer-based sensor. The purpose of this invention is to develop a nanoparticle-based aptamer sensor and use the p53 bioreceptor for cancer diagnosis with high sensitivity in the shortest time. In this regard, a DNA aptamer-based sensor was used on a glassy carbon electrode coated with gold nanoparticles / graphene oxide / conductive polymer . This sensor was created by the gold nanoparticles / aptamer-toluidine blue enhancer. The results obtained under optimal conditions of electrochemical investigation using amperometry indicated a detection limit of 0.29 picograms / mL in phosphate buffer and 0.341 picograms / mL in human blood plasma and a linear range of 1 to 300 picograms / mL for the sensor. This invention demonstrates the excellent and controllable performance of a modified carbon electrode to create a suitable sensor for detecting the cancer marker p53 protein.

The invention discloses a near-infrared AIE fluorescent probe based on a tetraphenylethylene-thiophene-indolium structure as well as a preparation method and application of the near-infrared AIE fluorescent probe. According to the preparation method, 5-(4-(1, 2, 2-triphenyl vinyl) phenyl) thiophene-2-formaldehyde (a reactant A) and 1-ethyl-2, 3, 3-trimethyl-3H-indolium iodide (a reactant B) are taken as raw materials, and the tetraphenyl ethylene-thiophene-indolium derivative (formula I) is prepared. The tetraphenylethylene-thiophene-indolium derivative has the characteristics of near infrared emission and aggregation-induced emission (AIE), can be used for real-time biological imaging and degradation of mutant p53 protein, and has a good application prospect in the aspect of developing tumor diagnosis and treatment integrated products.

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.

Provided herein, in some embodiments, are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a STAT3 inhibitor.

Solutions to the problem of the invention are a method for selectively killing or removing a senescent cell, substance identification, and a method for purifying a senescent cell. Specifically, the invention includes an agent for removing a senescent cell, which is a drug for removing an in vivo senescent cell, the agent containing an inhibitor for glutaminase as an active ingredient, and a pharmaceutical composition containing the agent. The invention further includes a method for preparing a senescent cell, including the following steps (a) to (c): (a) synchronizing a cell with the G2 phase; (b) activating an intracellular p53 protein in the cell synchronized with the G2 phase; and (c) inhibiting polo-like kinase 1 (PLK1) activity in the cell treated in the step (b).

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 invention discloses a series of polypeptides that specifically recognize and bind to the DDX24 helicase and their applications. The polypeptide sequences include the following amino acid signatures: 1. N-terminal-SQETFSDLWKLLPEN-carboxyl terminus; 2. N-terminal-S(p)QET(p)FSDLWKLLPEN-carboxyl terminus; 3. N-terminal-LTFEHYWAQLTS-carboxyl terminus, where the English letters represent common natural amino acids and (p) represents phosphorylation of the hydroxyl group of S or T. Currently, no polypeptides specifically recognize DDX24. The present polypeptides, derived from the p53 protein transcriptional domain, demonstrate for the first time that these polypeptides can specifically bind and recognize the DDX24 helicase.

A method may include a method for aiding in preventing breast cancer in a subject having a heterozygous germline mutation in BRCA1 or BRCA2, comprising: a. identifying a subject having a heterozygous germline mutation in BRCA1 or BRCA2; b. administering to the subject a therapeutically effective amount of a P53 protein stabilizer, wherein the P53 protein stabilizer comprises an MDM2 inhibitor.

The application provides a mouse fertilized ovum, wherein a sequence shown in SEQ ID NO. 1 in the fifth exon of a Trp53 gene is replaced by a fluorescent protein gene, and the individual developed from the fertilized ovum is a transgenic mouse for in-vivo labeling of p53 protein, and a construction method of the aforementioned fertilized ovum and transgenic mouse is provided. Through expression of the p53 and fluorescent label fusion protein, the application realizes accurate in-vivo labeling of the p53 protein, directly reflects the level of the p53 protein, and can track and analyze and sort abnormal cells by using flow cytometry according to the fluorescent protein label, so as to realize analysis and monitoring of tumor cell characteristics and tumor development process.

The application belongs to the technical field of biological medicine, and particularly relates to a polypeptide chimera targeting p53 protein stability and a preparation method and application thereof. The polypeptide chimera is a full polypeptide structure, which is connected by a USP7 recruiting domain, a p53 binding domain and a polypeptide linker containing an arginine chain, and has a general structure of A-L-B. The chimera can induce endogenous USP7 and p53 to be spatially adjacent as a molecular bridge, specifically removes the polyubiquitin chain of p53, up-regulates the p53 protein level in a concentration and time-dependent manner, prolongs the half-life of the p53 protein, activates the p21 downstream anticancer pathway, and the effect strictly depends on USP7. The chimera has high biological safety, is simple to synthesize, and provides a new strategy for the treatment of p53 function loss related tumors.

The invention relates to the technical field of nano-drugs, in particular to a difunctional nano-drug based on an autophagy targeting chimera-T cell connector as well as a preparation method and application of the difunctional nano-drug. The bifunctional nano-drug comprises a lipid shell, and an anti-CD3 antibody is coupled to the lipid shell; a T cell receptor targeting mutant p53 protein is inserted into the lipid shell; a medicine KPY is encapsulated in the lipid shell; and PFP is also encapsulated in the lipid shell. The nano-drug specifically recognizes a KRAS / TP53 mutant tumor through a surface-anchored T cell receptor, and low-intensity focused ultrasound is utilized to promote phase change of PFP to realize release of KPY at a tumor site so as to induce degradation of intracellular KRAS; and the CD3 antibody activates the CD8 + T cells to generate an extracellular immune activation effect. According to the technical scheme, the technical problem that in the prior art, targeted drugs for KRAS / TP53 co-mutation related tumors are lacked can be solved, and ideal application and popularization prospects are achieved.

Disclosed herein are gene editing systems comprising chemically modified RNAs (modRNAs) encoding Cas endonucleases or base editors. Wherein a gene editing system comprising a first chemically modified RNA (modRNA) comprising a sequence encoding a CRISPRassociated (Cas) endonuclease or a base editor; and a second modRNA comprising a sequence encoding a mutated p53 protein, wherein the mutated p53 protein inhibits a wild type p53 protein from binding to a target domain thereof.

The application provides a construction method and application of a mouse spontaneous tumor model of gastric cancer, and the construction method comprises the following steps: reducing or inhibiting the expression amount of a TP53 gene and / or the activity of a P53 protein in a mouse, and then chemically inducing the mouse by using a drug to obtain a mouse spontaneous tumor model of gastric cancer; wherein the drug comprises sodium nitrite and ethyl sarcosine, and / or the drug comprises an N-nitroso compound. The application first proposes to use NESS to construct a spontaneous gastric cancer model of a C57 mouse, and the construction method of the mouse spontaneous tumor model of gastric cancer provided by the application has a tumor formation rate of 75% or more; the tumor formation cycle is short, about 3-4 months, and the construction cost is low.

The present invention discloses a metal platinum complex with dual targeting of mitochondria and cell nuclei, as well as a preparation method and application thereof. The metal platinum complex with dual targeting of mitochondria and cell nuclei is obtained by combining cisplatin with a molecule containing a mitochondrial targeting group. The complex of the present invention can effectively inhibit the proliferation of human tumor cells, induce mitochondrial and DNA damage in tumor cells, and induce cancer cell death through mitochondrial autophagy and necrosis. In addition, the complex of the present invention can degrade mutant p53 protein, thereby eliminating the acquired function phenotype associated with mutant p53, including significantly inhibiting tumor growth, invasion and drug resistance, and has broad application prospects.