33 results about "Hsp90" patented technology

The present invention relates to a novel compound selected from a protein degrader or conjugate including a PI3K target moiety and an HSP90 target moiety linked through a linker, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof. The compound can treat cancer through a degradation pathway of a heat shock protein conjugate.

The application discloses a kind of 2-triazole ethane-1-ketone / alcohol HSP90 / HIF-1 inhibitor and application, new drug use technical field.This kind of inhibitor is transformed from 7-hydroxy new piece helicon A, can low toxicity efficiently inhibit the expression of HIF-1, inhibit tumor cell invasion, clonal proliferation and other malignant development process, in vivo anti-tumor activity experiment and cisplatin can effectively inhibit tumor.This kind of inhibitor can be applied to the preparation of inhibiting cancer development drug.

The invention relates to the technical field of aquaculture disease prevention and control and molecular biology, in particular to an RNA interference agent for killing ichthyophthirius multifilis, a preparation method, a composition and application. The interference agent is dsRNA / siRNA / shRNA or an expression vector of the dsRNA / siRNA / shRNA of targeted EF1-alpha, HSP90, ICP1 and ICP2; t7 tailed primer amplification, in-vitro transcription and annealing are adopted to prepare dsRNA, the dsRNA can be further prepared into a water body treatment composition with liposomes / chitosan and other carriers, and soaking treatment (20-28 DEG C, 1-48 h) is carried out in a grazing body stage. Under the conditions of 1 mu g / mL, 25 DEG C and 24 hours, the expression of the target gene is obviously reduced (2-delta delta Ct is less than or equal to 0.55), and the corrected death rates of 40.16% (EF1-alpha), 45.51% (HSP90), 21.39% (ICP < 1 >) and 19.39% (ICP < 2 >) are obtained. The scheme is green, has low residue, can be engineered, and is suitable for preposed blocking of the white-spot disease transmission chain in aquaculture.

Described herein are engineered platelets including a platelet cell or platelet-derived microparticle loaded with an HSP90 anchoring chimera including a protein of interest (POI) ligand covalently linked to a heat shock protein 90 (HSP90). The POI can be an intracellular or extracellular POI. Also described are methods of making the engineered platelets, and methods of degrading intracellular and extracellular POIs at a disease site.

This invention discloses a monoclonal antibody targeting HSP90 and its application. The monoclonal antibody targeting HSP90 can effectively inhibit the tumorigenicity and invasiveness of breast cancer cells, lung cancer cells, and osteosarcoma cells, and can significantly inhibit tumor growth in vivo. This invention provides a new targeted drug for diseases or symptoms related to high expression of HSP90, with broad prospects for clinical application.

The invention belongs to the technical field of biology, and particularly relates to an in-situ spray polymerization coating started by bacterial exovesicles (LBEVs) as well as a preparation method and application of the in-situ spray polymerization coating. And functionalizing the LBEVs by Fe < 3 + > through electrostatic adsorption to obtain an LBEVs-Fe < 3 + > solution. After LBEVs-Fe < 3 + > and pyrrole monomers are sprayed on a wound part, the LBEVs-Fe < 3 + > initiates pyrrole to be oxidized and polymerized into polypyrrole, and a polymerized coating LBEVs-PPy is formed. The LBEVs show effective antibacterial activity on staphylococcus aureus, escherichia coli and staphylococcus epidermidis, near-infrared triggered photo-thermal activation generates mild thermal therapy, expression of angiogenesis regulatory factors (such as VEGFA and ANGPT1) in human umbilical vein endothelial cells (HUVECs) is remarkably up-regulated, and an HSP90 / p-eNOS pathway is activated to accelerate angiogenesis, so that the activity of the LBEVs is improved. The LBEVs-PPy coating remarkably accelerates wound healing through a synergistic mechanism integrating the strong antibacterial activity of LBEVs and the efficient photo-thermal characteristic of PPy.

This invention relates to a compound based on CRBN ligand-induced ubiquitination degradation of Hsp90, its preparation method and uses, as shown in X-Y-Z, where X represents the ligand of HSP90 protein, Z represents the ligand of E3 ligase, and Y represents the chain connecting X and Z. This type of compound can be used to treat or prevent tumors.

Disclosed is an isolated antibody comprises: novel complementarity determining regions capable of specifically binding to the HSP90α epitope containing two EDK sites in the amino acid 235 to 244 and amino acid 251 to 260 regions, respectively. Also disclosed are nucleic acid molecules corresponding to the aforesaid antibody, a pharmaceutical composition comprising the aforesaid antibody or the corresponding nucleic acid molecules, and the methods for treating and monitoring a cancer using the aforesaid antibody.

The application discloses a chimeric body based on targeted degradation of GPX4 mediated by a molecular chaperone HSP90 and a preparation method and application thereof, and belongs to the technical field of biological medicines. Five chimeric bodies for targeted degradation of GPX4 are prepared by using the technology. The molecular chaperone HSP90 mediated protein targeted degradation chimeric body disclosed by the application can effectively induce degradation of GPX4, thereby triggering ferroptosis. Meanwhile, the chimeric body has obvious anti-proliferation activity on cell strains with high expression of GPX4, and has important significance for tumor targeted therapy.

The invention relates to the technical field of radiopharmaceuticals, and discloses a polypeptide compound targeting HSP90, a radioactive probe labeling precursor, a radioactive probe and a preparation method and application thereof, a T7 bacteriophage display polypeptide library is adopted to screen polypeptide specifically bound with HSP90, and the polypeptide compound targeting HSP90 is obtained; the method comprises the following steps: synthesizing a polypeptide compound targeting HSP90, mixing the polypeptide compound with a connecting arm and a chelating agent, carrying out a coupling reaction to obtain a labeled precursor crude product, and purifying to obtain a radioactive probe labeled precursor targeting HSP90; the nuclide eluent is eluted, then the nuclide eluent is mixed with the radioactive probe labeling precursor of the targeted HSP90, and after incubation, the radioactive probe of the targeted HSP90 is obtained. The radioactive molecular probe prepared by the invention can be specifically combined with HSP90 protein, has higher affinity and functional activity to HSP90, and can evaluate the expression level of HSP90 in vivo in real time.

The invention provides application of a targeted Hsp90 alpha compound in treatment of infectious encephalitis and improvement of clinical drug resistance, and belongs to the technical field of medicines. The targeted Hsp90 alpha compound disclosed by the invention has a structure as shown in a formula 1, and a parent nucleus structure of the targeted Hsp90 alpha compound is (3, 6, 6-trimethyl-4-oxo-4, 5, 6, 7-tetrahydro-1H-indazole-1-yl) benzamide. The targeted Hsp90 alpha compound can effectively treat infectious encephalitis, can treat infectious encephalitis caused by acyclovir and other nucleoside drug resistance viruses, and improves the clinical drug resistance problem of infectious encephalitis.

The invention provides application of a substance for inhibiting HSP90 alpha-K408 site lactic acid in astrocytes in epilepsy diseases. The HSP90 alpha-K408 site is the 408th site of an amino acid sequence shown in SEQ ID NO: 1. According to the invention, HSP90 alpha-K408 site lactic acid in astrocyte is taken as a treatment target of epilepsy, the polypeptide for inhibiting HSP90 alpha-K408 site lactic acid in astrocyte is provided, and mouse experiments prove that the polypeptide for inhibiting HSP90 alpha-K408 site lactic acid in astrocyte has an adjusting effect on the content of glutamic acid and glutamine; the number of neuronal cells can be effectively regulated and controlled, and epilepsy diseases can be effectively relieved and treated.

The present invention relates to a novel compound and anticancer uses thereof and, more specifically, provides: a novel compound exhibiting inhibitory activity against HSP90, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition for preventing or treating cancer diseases comprising same; and a health functional food composition for preventing or improving cancer diseases comprising the compound.

The present invention relates to a chromene-benzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient, the chromene-benzimidazole derivative of the present invention being activated in cancer cells, being capable of inhibiting tubulin polymerization and inhibiting a C-terminal domain of Hsp90, and being capable of preventing or treating cancer, or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient. When the compound is administered to a subject, cancer cell cycle arrest can be caused to induce cell apoptosis and hinder the activity of onco-protein, and the compound can be used as a novel double-targeting anti-cancer drug to prevent or treat cancers, preferably to prevent or treat triple negative breast cancer.

The expression of the ATXN2 gene can be modulated to reduce the amount of ataxin-2 protein produced by a cell. This can be accomplished by administering to the cell an effective amount of an ATXN2 modulating agent. Screening was performed with 428,749 compounds for lowering expression of an ATXN2-luciferase reporter in HEK-293 cells, with a multiplexed cell viability assay to ensure target reduction in the absence of cytotoxicity. Secondary qHTS assays included a CMV-luciferase reporter expressed in HEK-293 cells as well as a biochemical assay using recombinant luciferase to detect inhibitors of the reporter enzyme. A diverse set of compounds were found to reduce ATXN2 expression, including compounds targeting HSP90, cardiac glycosides, NaK-ATPases and topoisomerases.

This application relates to a cyanobacteria extract with photothermal damage repair effects, its preparation method, and its application, belonging to the field of cosmetic raw material technology. The cyanobacteria extract provided in this application can be used to balance the inflammatory and repair signaling pathways of skin cells after photothermal damage, and can be used to prepare skin care products with soothing, anti-inflammatory, and barrier-repair-promoting effects. It can synergistically balance the pro-inflammatory damage signaling pathway TLR4 / NF-κB axis and the survival-promoting repair signaling pathway HSP90 / PI3K-Akt axis simultaneously activated in skin cells after photothermal damage, targeting multiple points. This can more effectively control excessive inflammation, reduce secondary damage, and enhance the cell's self-repair ability. It is suitable for various scenarios such as sunburn, post-laser surgery, and thermal environment damage, and has significant technical advantages compared to existing technologies, with broad application prospects and huge market value.

The present disclosure relates to an anticancer vaccine composition including a peptide of SEQ ID NO: 1 and a peptide of SEQ ID NO: 2, which are epitopes of HSP90, and the vaccine composition according to the present disclosure may effectively inhibit the growth of tumors in an animal model of tumor cell line transplantation without severe adverse effects, and thus may be useful for treating cancer or preventing cancer recurrence.

The invention relates to a novel EZH2-HSP90 double-effect inhibitor for the first time, a preparation method of the EZH2-HSP90 double-effect inhibitor and application of the EZH2-HSP90 double-effect inhibitor to treatment of diseases / symptoms mediated by EZH2, HSP90 or the EZH2 and the HSP90, especially glioblastoma.

The invention relates to the technical field of biological medicines, in particular to a construction method and application of a tool mouse for specifically knocking out cre by germ cell genes, and the construction method is characterized in that a Cre recombinant sequence carrying a Ddx4 promoter sequence is knocked into a mouse genome safety site Hipp11 by virtue of a CRISPR-CAS9 technology so as to construct a Ddx4 Promoter-Kozak-CreERT2-rBGpA gene knock-in mouse model. The model mouse realizes the characteristic of specific expression of CreERT2 recombinase under the driving of a germ cell specific promoter Ddx4, the expressed CreERT2 protein is inactivated after the cell cytoplasm is combined with the HSP90 protein, the CreERT2 is dissociated after being induced by tamoxifen and enters a cell nucleus, and an Loxp sequence is cut to realize gene recombination. According to the invention, the exogenous sequence is inserted into the safe site of the genome, so that the expression and function of the original endogenous gene of the mouse are not influenced, the fertility of the male and female mice is not influenced, and the method has the advantages of high efficiency and convenience in subsequent gene knockout. The model mouse is expected to accelerate the analysis of the action mechanism for regulating the gametogenesis gene of the mouse.

Treatment of neurodegenerative diseases is achieved using small molecule purine scaffold compounds that inhibit Hsp90 and that possess the ability to cross the blood-brain barrier or are otherwise delivered to the brain.

The invention discloses a monoclonal antibody targeting HSP90 and application thereof, the monoclonal antibody targeting HSP90 can effectively inhibit tumorigenic ability and invasion ability of breast cancer cells, lung cancer cells and osteosarcoma cells, and can significantly inhibit growth of tumors in vivo, the invention provides a new targeting drug for diseases or symptoms related to high expression of HSP90, and the monoclonal antibody targeting HSP90 has good application prospects. The clinical application prospect is wide.

The present invention relates to: a chromene-benzimidazole derivative or a pharmaceutically acceptable salt thereof; and a composition for preventing or treating cancer, the composition comprising the derivative as an active ingredient. The chromene-benzimidazole derivative according to the present invention is activated in cancer cells to inhibit tubulin polymerization and suppress the C-terminal domain of Hsp90, thereby blocking the cell cycle of cancer cells, inducing apoptosis, and inhibiting the activity of oncoproteins, and thus can be used as a novel dual-target anticancer drug for preventing or treating cancer, preferably for preventing or treating triple-negative breast cancer.

The present application provides a compound shown in formula (I) and a prodrug thereof, the compound has good AHA1 inhibiting effect, can be used for treating HSP90-AHA1 mediated diseases and / or disorders, such as multiple myeloma and / or colorectal cancer, and preparing a medicine for the diseases or disorders. In particular, the compound containing a phenolic ester structure has higher bioavailability, as a prodrug, can release an AHA1 inhibitor with high activity in an animal body, and has good drug property.

Described herein are engineered platelets including a platelet cell or platelet-derived microparticle loaded with an HSP90 anchoring chimera including a protein of interest (POI) ligand covalently linked to a heat shock protein 90 (HSP90). The POI can be an intracellular or extracellular POI. Also described are methods of making the engineered platelets, and methods of degrading intracellular and extracellular POIs at a disease site.

A composition comprising N The application belongs to the technical field of pharmacy and chemical industry. The (hetero)aryl-substituted tetrahydroquinolines are prepared by the method N The (hetero)aryl-substituted tetrahydroquinolines are evaluated for their inhibitory effect on HIF-1 signaling pathway and in-vitro anti-proliferative activity. The results show that the five modified compounds exhibit excellent HIF-1 inhibitory activity and have low toxicity. Unexpectedly, the compound I-11 shows strong anti-proliferative activity with a half-inhibitory concentration of 5.4 μM. Surface plasmon resonance experiments show that the K D of the compound I-4 with human Hsp90α protein is 4.7 μM, proving that the action target of I-4 is Hsp90. The compound and its pharmaceutically acceptable salts have a broad application space in the preparation of anti-tumor drugs and HIF-1 inhibitors.

The present invention relates to a chromene-benzimidazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient, the chromene-benzimidazole derivative of the present invention being activated in cancer cells, being capable of inhibiting tubulin polymerization and inhibiting a C-terminal domain of Hsp90, and being capable of preventing or treating cancer, or a pharmaceutically acceptable salt thereof, and a composition for preventing or treating cancer comprising the derivative as an active ingredient. When the compound is administered to a subject, cancer cell cycle arrest can be caused to induce cell apoptosis and hinder the activity of protooncoprotein, and the compound can be used as a novel double-targeting anti-cancer drug to prevent or treat cancers, preferably to prevent or treat triple negative breast cancer.

The invention belongs to the technical field of plant genetic engineering, and discloses a heat shock protein gene HSP90-1 for improving cadmium stress resistance of cardamine violifolia and application of the heat shock protein gene HSP90-1. The gene is a selenium-cadmium co-regulation target which is identified for the first time from a leaf transcriptome of cardamine violifolia under cadmium stress, HSP90-1 protein coded by the gene can form a Se-S bond with nano-selenium to be competitively combined with cadmium ions so as to recover ATP enzyme activity and molecular chaperone functions of the gene, so that an anti-oxidation system and a photosynthetic protection pathway of cardamine violifolia are regulated and controlled, and the anti-oxidation effect of the cardamine violifolia is improved. The cadmium stress resistance is enhanced. Not only is basic cognition on a heavy metal detoxification mechanism deepened, but also a practical solution is provided for agricultural application such as cultivation of high-HSP90-1 expression low-cadmium varieties. The method does not need to depend on exogenous elements, the cadmium stress resistance of cardamine violifolia and the soil cadmium remediation efficiency can be stably improved, and new gene resources and technical means are provided for ecological remediation of cadmium pollution.

This invention belongs to the field of biotechnology, specifically relating to an in-situ spray-polymerized coating initiated by bacterial extravesicles (LBEVs), its preparation method, and its application. LBEVs are electrostatically adsorbed by Fe... 3+ Functionalization yields LBEVs-Fe 3+ Solution. Spray LBEVs-Fe onto the wound site. 3+ After reacting with pyrrole monomers, LBEVs-Fe 3+ The process initiates the oxidative polymerization of pyrrole to form polypyrrole, resulting in a polymeric coating LBEVs-PPy. The LBEVs of this invention exhibit effective antibacterial activity against Staphylococcus aureus, Escherichia coli, and Staphylococcus epidermidis. Near-infrared triggered photothermal activation produces mild thermotherapy, significantly upregulating the expression of angiogenesis regulators (such as VEGFA and ANGPT1) in human umbilical vein endothelial cells (HUVECs) and activating the HSP90 / p-eNOS pathway to accelerate angiogenesis. The LBEVs-PPy coating significantly accelerates wound healing through a synergistic mechanism integrating the potent antibacterial activity of LBEVs and the highly efficient photothermal properties of PPy.

The application discloses a compound which can be used for a novel HSP90 and HDAC double-target inhibitor, and a structural general formula is shown as formula I: wherein R1 is selected from an alkyl group or an aromatic group, R2 is selected from a C1-C3 alkyl group, and L is selected from a substituted phenyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a furanyl group, a thiophenyl group, a thiazolyl group and an isoxazolyl group. The application provides a novel compound which can be used for a novel HSP90 and HDAC double-target inhibitor, can simultaneously inhibit HSP90 and HDAC activities, can play a synergistic role in disease treatment, and has strong therapeutic activity.

The present invention relates to an inhibitor of heat shock protein 90. Disclosed are a heat shock protein 90-based bivalent inhibitor, and a preparation method therefor and the use thereof. The bivalent inhibitor is a compound having a structural formula as shown in formula I: A-L-B Formula I, or a pharmaceutically acceptable salt, solvate, or optical isomer thereof, wherein A and B are ATP inhibitors of heat shock protein 90, and the motif structure of L is a flexible linker group of PEG or alkanes, or a rigid linker group comprising aryl, heteroalkyl, or heteroaryl. The bivalent inhibitor can effectively inhibit the activity of molecular chaperone HSP90, hinder the folding and modification of a substrate protein, degrade the substrate protein via a ubiquitin-proteasome degradation pathway, induce non-native dimerization of HSP90, and interfere with protein-protein interactions associated with HSP90. In addition, the bivalent inhibitor reduces the heat shock response induced by HSP90 inhibition, and exhibits potent activity in degrading the substrate protein.